which step of eukaryotic mrna processing helps in the initiation of translation
capping
3030446
Five-prime cap In molecular biology, the five-prime cap (5′ cap) is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation of stable and mature messenger RNA able to undergo translation during protein synthesis. Mitochondrial mRNA and chloroplastic mRNA are not capped. In eukaryotes, the 5′ cap (cap-0), found on the 5′ end of an mRNA molecule, consists of a guanine nucleotide connected to mRNA via an unusual 5′ to 5′ triphosphate linkage. This guanosine is methylated on the
Five-prime cap
8718188
the cap to the mRNA while it is produced by RNA polymerase II. Eukaryotic RNA must undergo a series of modifications in order to be exported from the nucleus and successfully translated into function proteins, many of which are dependent on mRNA capping, the first mRNA modification to take place. 5' capping is essential for mRNA stability, enhancing mRNA processing, mRNA export and translation. After successful capping, an additional phosphorylation event initiates the recruitment of machinery necessary for RNA splicing, a process by which introns are removed to produce a mature mRNA. The addition of the cap onto mRNA confers
Capping enzyme
6557190
out in separate compartments of the cell (the nucleus and cytoplasm). Eukaryotic mRNA precursors must be processed in the nucleus (e.g., capping, polyadenylation, splicing) before they are exported to the cytoplasm for translation. Translation can also be affected by ribosomal pausing, which can trigger endonucleolytic attack of the mRNA, a process termed mRNA no-go decay. Ribosomal pausing also aids co-translational folding of the nascent polypeptide on the ribosome, and delays protein translation while it is encoding mRNA. This can trigger ribosomal frameshifting. Termination of elongation depends on eukaryotic release factors. The process is similar to that of prokaryotic termination, but
Eukaryotic translation
4187256
types of encoded messages that lead to translation of various types of products. Furthermore, primary transcript processing provides a control for gene expression as well as a regulatory mechanism for the degradation rates of mRNAs. The processing of pre-mRNA in eukaryotic cells includes 5' capping, 3' Polyadenylation, and alternative splicing. Shortly after transcription is initiated in eukaryotes, a pre-mRNA's 5' end is modified by the addition of a 7-methylguanosine cap, also known as a 5' cap. The 5' capping modification is initiated by the addition of a GTP to the 5' terminal nucleotide of the pre-mRNA in reverse orientation followed
Primary transcript
11183808
Eukaryotic translation initiation factor 4 gamma 1 Eukaryotic translation initiation factor 4 gamma 1 is a protein that in humans is encoded by the "EIF4G1" gene. The protein encoded by this gene is a component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure, and recruitment of mRNA to the ribosome. Alternative splicing results in five transcript variants encoding four distinct isoforms. eIF4G serves as a scaffold, interacting with mRNA and the other components of the eIF4F complex, as well as the PABP and eIF3. Eukaryotic translation initiation
Eukaryotic translation initiation factor 4 gamma 1
11183809
factor 4 gamma has been shown to interact with MKNK1, EIF4A1, EIF4E, MKNK2 and PABPC1. Eukaryotic translation initiation factor 4 gamma 1 Eukaryotic translation initiation factor 4 gamma 1 is a protein that in humans is encoded by the "EIF4G1" gene. The protein encoded by this gene is a component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure, and recruitment of mRNA to the ribosome. Alternative splicing results in five transcript variants encoding four distinct isoforms. eIF4G serves as a scaffold, interacting with mRNA and the other
Eukaryotic translation initiation factor 4 gamma 1
6557182
Eukaryotic translation Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recycling. Initiation of translation usually involves the interaction of certain key proteins, the initiation factors, with a special tag bound to the 5'-end of an mRNA molecule, the 5' cap, as well as with the 5' UTR. These proteins bind the small (40S) ribosomal subunit and hold the mRNA in place. eIF3 is associated with the 40S ribosomal subunit and plays a role in keeping the large (60S) ribosomal subunit from prematurely binding.
Eukaryotic translation
6557192
protein domains in their readthrough extension so that new protein isoforms can arise. This process has been termed 'functional translational readthrough'. Eukaryotic translation Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recycling. Initiation of translation usually involves the interaction of certain key proteins, the initiation factors, with a special tag bound to the 5'-end of an mRNA molecule, the 5' cap, as well as with the 5' UTR. These proteins bind the small (40S) ribosomal subunit and hold the mRNA in place. eIF3
Eukaryotic translation
17073951
This complex then binds to the 5' cap of mRNA and will recruit the helicase eukaryotic translation initiation factor A (eIF4A) and its cofactor eukaryotic translation initiation factor 4B (eIF4B). The helicase is required to remove hairpin loops that arise in the 5' untranslated regions of mRNA, which prevent premature translation of proteins. Once the initiation complex is assembled at the 5' cap of mRNA, it will recruit the 40S small ribosomal subunit that is now capable of scanning for the AUG start codon start site, because the hairpin loop has been eradicated by the eIF4A helicase. Once the ribosome
MTORC1
11354081
EIF3D Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a protein that in humans is encoded by the "EIF3D" gene. Eukaryotic translation initiation factor-3 (eIF3), the largest of the eIFs, is a multiprotein complex composed of at least ten nonidentical subunits. The complex binds to the 40S ribosome and helps maintain the 40S and 60S ribosomal subunits in a dissociated state. It is also thought to play a role in the formation of the 40S initiation complex by interacting with the ternary complex of eIF2/GTP/methionyl-tRNA, and by promoting mRNA binding. The protein encoded by this gene is the major
EIF3D
6557188
be trafficked to the start site by direct binding, initiation factors, and/or ITAFs (IRES trans-acting factors) bypassing the need to scan the entire 5' UTR. This method of translation has been found important in conditions that require the translation of specific mRNAs during cellular stress, when overall translation is reduced. Examples include factors responding to apoptosis and stress-induced responses. Elongation depends on eukaryotic elongation factors. At the end of the initiation step, the mRNA is positioned so that the next codon can be translated during the elongation stage of protein synthesis. The initiator tRNA occupies the P site in the
Eukaryotic translation
20369052
neurons contribute to neuronal plasticity and help prevent neuronal degradation. Small, non-coding RNAs such as BC200 RNA work to repress translation by inhibiting its initiation. During eukaryotic translation, the preinitiation complex binds mRNA and scans the coding strand for a start codon. This step is often subject to the control of a family of initiation factors and these factors are often a target for translational regulators. Poly(A)-binding protein (PABP) has been shown to bind to BC200 RNA further confirming their role as regulators of protein biosynthesis in synapses. BC200 RNA targets an ATP-dependent RNA helicase called eukaryotic initiation factor 4A
BC200 lncRNA
9717322
Eukaryotic initiation factor Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNA called the 43S preinitiation complex (43S PIC). Additional factors of the eIF4F complex (eIF4A, E, and G) recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG
Eukaryotic initiation factor
17073950
in the mitochondria under hypoxic stress or hypoxia, AMPK will also become active and thus inhibit mTORC1 through its processes. mTORC1 activates transcription and translation through its interactions with p70-S6 Kinase 1 (S6K1) and 4E-BP1, the eukaryotic initiation factor 4E (eIF4E) binding protein 1. Their signaling will converge at the translation initiation complex on the 5' end of mRNA, and thus activate translation. Activated mTORC1 will phosphorylate translation inhibitor 4E-BP1, releasing it from eukaryotic translation initiation factor 4E (eIF4E). eIF4E is now free to join the eukaryotic translation initiation factor 4G (eIF4G) and the eukaryotic translation initiation factor 4A (eIF4A).
MTORC1
12014943
the complementarity of tRNA and mRNA in protein translation. It is the largest component of several translation initiation complexes, including the 43S and 48S preinitiation complexes (PICs), being bound by several eukaryotic initiation factors, including eIF1, eIF1A, and eIF3. The 40S ribosomal subunit is also tightly bound by the HCV IRES to form a binary complex mediate by protein-mRNA and rRNA-mRNA interactions. More information can be found in the articles on the ribosome, the eukaryotic ribosome (80S), and the article on protein translation. The shape of the small subunit can be subdivided into two large segments, the head and the
Eukaryotic small ribosomal subunit (40S)
9717323
start codon. Recognition of the start codon by the Met-tRNA promotes gated phosphate and eIF1 release to form the 48S preinitiation complex (48S PIC), followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors, reflecting the greater biological complexity of eukaryotic translation. There are at least twelve eukaryotic initiation factors, composed of many more polypeptides, and these are described below. eIF1 and eIF1A both bind to the 40S ribosome subunit-mRNA complex. Together they induce an "open" conformation of the mRNA binding channel, which is crucial for scanning,
Eukaryotic initiation factor
6557189
ribosome, and the A site is ready to receive an aminoacyl-tRNA. During chain elongation, each additional amino acid is added to the nascent polypeptide chain in a three-step microcycle. The steps in this microcycle are (1) positioning the correct aminoacyl-tRNA in the A site of the ribosome, (2) forming the peptide bond and (3) shifting the mRNA by one codon relative to the ribosome. Unlike bacteria, in which translation initiation occurs as soon as the 5' end of an mRNA is synthesized, in eukaryotes such tight coupling between transcription and translation is not possible because transcription and translation are carried
Eukaryotic translation
12232504
EIF4G Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast, and wheat. However, eIF4G is exclusively found in domain Eukarya, and not in domains Bacteria or Archaea, which do not have capped mRNA. As such, eIF4G structure and function may vary between species, although the human eIF4G 1 has been the focus of extensive studies. Across species, eIF4G strongly associates with eIF4E, the protein that directly binds the mRNA cap. Together with the
EIF4G
9717331
but binds with the large subunit. Eukaryotic initiation factor Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNA called the 43S preinitiation complex (43S PIC). Additional factors of the eIF4F complex (eIF4A, E, and G) recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along
Eukaryotic initiation factor
11147704
and mRNA interactions at synapse(s) through its recruitment of FMRP to the appropriate mRNA. In addition, FMRP may recruit CYFIP1 to specific mRNAs in order to repress translation. The FMRP-CYFIP1 translational inhibitor is regulated by stimulation of neuron(s). Increased synaptic stimulation resulted in the dissociation of eIF4E and CYFIP1, allowing for the initiation of translation. EIF4E has been shown to interact with: EIF4E Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the "EIF4E" gene. Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine five-prime cap structure, m7GpppX
EIF4E
11153158
and independent translation, the eIF4G2 gene product functions as a general repressor of translation by forming translationally inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. EIF4G2 has been shown to interact with EIF3A. EIF4G2 Eukaryotic translation initiation factor 4 gamma 2 (also called p97, NAT1, and DAP-5) is a protein that in humans is encoded by the "EIF4G2" gene. Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation
EIF4G2
11138884
and activation of cap-dependent mRNA translation. EIF4EBP1 has been shown to interact with: EIF4EBP1 Eukaryotic translation initiation factor 4E-binding protein 1 (also known as 4E-BP1) is a protein that in humans is encoded by the "EIF4EBP1" gene. This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various
EIF4EBP1
269930
begins with transcription, and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic mRNA molecules do not. A molecule of eukaryotic mRNA and the proteins surrounding it are together called a messenger RNP. Transcription is when RNA is made from DNA. During transcription, RNA polymerase makes a copy of a gene from the DNA to mRNA as needed. This process is similar in eukaryotes and prokaryotes. One notable difference, however, is that eukaryotic RNA polymerase associates with mRNA-processing
Messenger RNA
17110981
Cap-independent translation element In molecular biology, a cap-independent translation element (CITE or 3'CITE) is an RNA sequence found in the 3'UTR of many RNA plant viruses. Eukaryotic mRNAs contain a 5' cap structure which is required for efficient binding of translation initiation factors. Many viral mRNAs lack the 5' cap, animal virus mRNAs often contain an internal ribosome entry site which functions in translation initiation. Many plant viral mRNAs contain a cap-independent translation element. These elements mediate initiation of translation of the proteins encoded in the mRNA by either recruiting translation inititation factors or the 60S ribosomal subunit to the
Cap-independent translation element
9717327
eIF2 heterotrimer and they seem to play unique functions in translation. Instead, they appear to be involved in specialized pathways, such as 'eIF2-independent' translation initiation or re-initiation, respectively. eIF3 independently binds the 40S ribosomal subunit, multiple initiation factors, and cellular and viral mRNA. In mammals, eIF3 is the largest initiation factor, made up of 13 subunits (a-m). It has a molecular weight of ~800 kDa and controls the assembly of the 40S ribosomal subunit on mRNA that have a 5' cap or an IRES. eIF3 may use the eIF4F complex, or alternatively during internal initiation, an IRES, to position the
Eukaryotic initiation factor
11147697
EIF4E Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the "EIF4E" gene. Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine five-prime cap structure, m7GpppX (where X is any nucleotide). This structure is involved in several cellular processes including enhanced translational efficiency, splicing, mRNA stability, and RNA nuclear export. eIF4E is a eukaryotic translation initiation factor involved in directing ribosomes to the cap structure of mRNAs. It is a 24-kD polypeptide that exists as both a free form and as part of the eIF4F pre-initiation complex. Almost
EIF4E
12691925
take effect. Eukaryotic initiation factor complex 2 (eIF2) forms a ternary complex with GTP and the initiator Met-tRNA – this process is regulated by guanine nucleotide exchange and phosphorylation and serves as the main regulatory element of the bottleneck of gene expression. Before translation can progress to the elongation stage, a number of initiation factors must facilitate the synergy of the ribosome and the mRNA and ensure that the 5’ UTR of the mRNA is sufficiently devoid of secondary structure. Binding in this way is facilitated by group 4 eukaryotic initiation factors; eIF4F has implications in the normal regulation of
EIF4A
13624774
Red clover necrotic mosaic virus translation enhancer elements Red clover necrotic mosaic virus (RCNMV) contains several structural elements present within the 3' and 5' untranslated regions (UTR) of the genome that enhance translation. In eukaryotes transcription is a prerequisite for translation. During transcription the pre-mRNA transcript is processes where a 5' cap is attached onto mRNA and this 5' cap allows for ribosome assembly onto the mRNA as it acts as a binding site for the eukaryotic initiation factor eIF4F. Once eIF4F is bound to the mRNA this protein complex interacts with the poly(A) binding protein which is present within
Red clover necrotic mosaic virus translation enhancer elements
10294466
Luteovirus cap-independent translation element The Barley yellow dwarf virus-like cap-independent translation element (BTE) is an RNA element found in the 3' UTR of some luteoviruses. This element mediates translation of genomic RNA and subgenomic RNA1 (sgRNA1). BTEs have a consensus sequence, GGAUCCUGGGAAACAGG, embedded in series of three to six stem-loops that radiate from a central hub. BTE has been found to bind to eIF4G and weakly to eIF4E (proteins involved in translation initiation). BTE allows translation initiation of an mRNA without a 7mG cap (required for translation in most eukaryotic mRNA). Other forms of cap-independent translation elements (CITE) exist (primarily
Luteovirus cap-independent translation element
1391890
the RNA from decapping. Another modification is 3' "cleavage and polyadenylation". They occur if polyadenylation signal sequence (5'- AAUAAA-3') is present in pre-mRNA, which is usually between protein-coding sequence and terminator. The pre-mRNA is first cleaved and then a series of ~200 adenines (A) are added to form poly(A) tail, which protects the RNA from degradation. Poly(A) tail is bound by multiple poly(A)-binding proteins (PABP) necessary for mRNA export and translation re-initiation. A very important modification of eukaryotic pre-mRNA is "RNA splicing". The majority of eukaryotic pre-mRNAs consist of alternating segments called exons and introns. During the process of splicing,
Gene expression
4220378
levels of transcript available to be translated by ribosomes. There are two main requirements for mRNA degradation to take place: mRNA degradation is localised in cytoplasmic bodies called P-bodies. RISC can modulate the loading of ribosome and accessory factors in translation to repress expression of the bound mRNA transcript. Translational repression only requires a partial sequence match between the guide strand and target mRNA. Translation can be regulated at the initiation step by: Translation can be regulated at post-initiation steps by: There is still speculation on whether translational repression via initiation and post-initiation is mutually exclusive. Some RISCs are able
RNA-induced silencing complex
13994925
new proteins, the ribosome being the major target. Kasugamycin inhibits protein synthesis at the step of translation initiation. Kasugamycin inhibition is thought to occur by direct competition with initiator transfer RNA. Recent experiments suggest that kasugamycin indirectly induces dissociation of P-site-bound fMet-tRNA from 30S subunits through perturbation of the mRNA, thereby interfering with translation initiation. Kasugamycin specifically inhibits translation initiation of canonical but not of leaderless mRNA. For initiation on leaderless mRNA, the overlap between mRNA and kasugamycin is reduced and the binding of tRNA is further stabilized by the presence of the 50S subunit, minimizing Ksg efficacy. Kasugamycin also
Kasugamycin
10294346
the mRNA). HCV IRES independently binds two components of eukaryotic translation initiation machinery, the multiprotein initiation factor eIF3 and 40S small ribosomal subunit. Moreover, it binds 40S in such a manner that AUG initiator codon is positioned in the ribosomal P-site, thus no ribosomal scanning is required. Consequently scanning factors eIF1 and eIF1A are dispensable for the HCV translation, as are components of the eIF4F complex (eIF4A, eIF4E, and eIF4G) and eIF4B, which are generally required for mRNA binding and unwinding of 5'UTR. Initiator tRNA is delivered either by eIF2 or, in stress conditions when eIF2 is inactivated, by eIF2A,
Hepatitis C virus internal ribosome entry site
6200770
is located between two reporter open reading frames in a eukaryotic mRNA molecule (a bicistronic mRNA), it can drive translation of the downstream protein coding region independently of the 5'-cap structure bound to the 5' end of the mRNA molecule. In such a setup,both proteins are produced in the cell. The first reporter protein located in the first cistron is synthesized by the cap-dependent initiation, while translation initiation of the second protein is directed by the IRES element located in the intercistronic spacer between the two reporter protein coding regions. However, there are several caveats to be aware of when
Internal ribosome entry site
13479035
Leaky scanning Leaky scanning is a mechanism used during the initiation phase of Eukaryotic translation that enables regulation of gene expression. During initiation, the small 40S ribosomal subunit (as a 43S PIC) "scans" or moves in a 5' --> 3' direction along the 5'UTR to locate a start codon to commence elongation. Sometimes, the scanning ribosome bypasses the initial AUG start codon and begins translation at further downstream AUG start codons. Translation in eukaryotic cells according to most scanning mechanisms occurs at the AUG start codon proximal to the 5' end of mRNA; however, the scanning ribosome may encounter an
Leaky scanning
11092731
rotavirus infection PABP is evicted from eIF4G, probably impairing the translation of polyadenylated mRNA and leading to the shutoff of cellular mRNA translation observed during rotavirus infection. Rotavirus translation Rotavirus translation, the process of translating mRNA into proteins, occurs in a different way in Rotaviruses. Unlike the vast majority of cellular proteins in other organisms, in Rotaviruses the proteins are translated from capped but nonpolyadenylated mRNAs. The viral nonstructural protein NSP3 specifically binds the 3'-end consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIF4G. The Rotavirus replication cycle occurs entirely in the cytoplasm. Upon virus
Rotavirus translation
19341177
of the complex are also involved in cap-independent translation initiation; for instance, certain viral proteases cleave eIF4G to remove the eIF4E-binding region, thus inhibiting cap-dependent translation. Structures of eIF4F components have been solved individually and as partial complexes by a variety of methods, but no complete structure of eIF4F is currently available. In mammals, the eIF4E•G•A trimeric complex can be directly purified from cells, while only the two subunit eIF4E•G can be purified from yeast cells. eIF4E binds the mG 5' cap and the eIF4G scaffold, connecting the mRNA 5' terminus to a hub of other initiation factors and mRNA.
Eukaryotic initiation factor 4F
13759941
ACAT1 mRNA Human acetyl-coA cholesterol acyltransferase (ACAT1) gene produces a chimeric mRNA through the interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7. This chimeric mRNA uses AUG as a translation initiation codon to produce the normal 50-kDa ACAT1 protein but used an alternative translation initiation codon, GGC, to produce the novel enzymatically active 56-kDa isoform. Mutagenesis and mass spectrometry identified the alternative initiation codon as the start codon for the novel 56-kDa protein and its location was mapped to a region located upstream of the AUG initiation codon. Three stem loop structures have been predicted to
ACAT1 mRNA
10294347
eIF2D, or possibly eIF5B, a homologue of prokaryotic IF2 protein. Hepatitis C virus internal ribosome entry site The Hepatitis C virus internal ribosome entry site, or HCV IRES, is an RNA structure within the 5'UTR of the HCV genome that mediates cap-independent translation initiation. Protein translation of most eukaryotic mRNAs occurs by a cap-dependent mechanism and requires association of Met-tRNA, several eukaryotic initiation factors, and GTP with the 40S ribosomal subunit, recruitment to the 5' cap, and scanning along the 5' UTR to reach to start codon. In contrast, translation of hepatitis C virus (HCV) mRNA is initiated by a
Hepatitis C virus internal ribosome entry site
10294344
Hepatitis C virus internal ribosome entry site The Hepatitis C virus internal ribosome entry site, or HCV IRES, is an RNA structure within the 5'UTR of the HCV genome that mediates cap-independent translation initiation. Protein translation of most eukaryotic mRNAs occurs by a cap-dependent mechanism and requires association of Met-tRNA, several eukaryotic initiation factors, and GTP with the 40S ribosomal subunit, recruitment to the 5' cap, and scanning along the 5' UTR to reach to start codon. In contrast, translation of hepatitis C virus (HCV) mRNA is initiated by a different mechanism from the usual 5' cap-binding model. This alternate
Hepatitis C virus internal ribosome entry site
12691926
translation as well as the transformation and progression of cancerous cells; as such, it represents an interesting field of research. The repertoire of compounds involved in eukaryotic translation consists of initiation factor classes 1 – 6; eIF4F is responsible for the binding of capped mRNA to the 40S ribosomal subunit via eIF3. The mRNA cap is bound by eIF4E (25 kDa), eIF4G (185 kDa) acts as a scaffold for the complex whilst the ATP-dependent RNA helicase eIF4A (46 kDa) processes the secondary structure of the mRNA 5’ UTR to render it more conducive to ribosomal binding and subsequent translation. Together
EIF4A
20682365
site, helping the unambiguous placement of tRNAi in the P site of in the large ribosomal subunit. The main function of archaeal IF2 is to join the ribosomal subunits (small and large) to form the complete single (monomeric) mRNA bound ribosome unit in the late stages of initiation. The a/eIF2 binds to the 40S small subunit of the ribosome to help guide the start translation of mRNA into proteins. Archaeal initiation factors Archaeal initiation factors are proteins that are used during the translation step of protein synthesis in archaea. The principal functions these proteins perform include ribosome RNA/mRNA recognition, delivery
Archaeal initiation factors
3925349
Vivo-Morpholinos, in which the oligo is covalently linked to a delivery dendrimer, enter cells when administered systemically in adult animals or in tissue cultures. In eukaryotic organisms, pre-mRNA is transcribed in the nucleus, introns are spliced out, then the mature mRNA is exported from the nucleus to the cytoplasm. The small subunit of the ribosome usually starts by binding at the 5' end end of the mRNA and is joined there by various other eukaryotic initiation factors, forming the initiation complex. The initiation complex scans along the mRNA strand until it reaches a start codon, and then the large subunit
Morpholino
19357151
43S preinitiation complex The 43S preinitiation complex (43S PIC) is a ribonucleoprotein complex that exists during an early step of eukaryotic translation initiation. The 43S PIC contains the small ribosomal subunit (40S) bound by the initiation factors eIF1, eIF1A, eIF3, and the eIF2-Met-tRNA-GTP ternary complex (eIF2-TC). The 43S is an important intermediate complex during cap-dependent translation initiation. In the canonical model of translation initiation, the 43S PIC is pre-formed as a stable complex and recruited to the 5' cap of eukaryotic messenger RNAs (mRNAs) by the eIF4F complex. The 43S PIC then "scans" in the 5' --> 3' direction along
43S preinitiation complex
7197511
P-bodies Processing bodies (P-bodies) are distinct foci within the cytoplasm of the eukaryotic cell consisting of many enzymes involved in mRNA turnover. P-bodies have been observed in somatic cells originating from vertebrates and invertebrates, plants and yeast. To date, P-bodies have been demonstrated to play fundamental roles in general mRNA decay, nonsense-mediated mRNA decay, adenylate-uridylate-rich element mediated mRNA decay, and microRNA induced mRNA silencing. Not all mRNAs which enter P-bodies are degraded, as it has been demonstrated that some mRNAs can exit P-bodies and re-initiate translation. Purification and sequencing of the mRNA from purified processing bodies showed that these mRNAs
P-bodies
6557187
yeast meiosis and ethylene response in plants. In addition, recent work in yeast and humans suggest that evolutionary divergence in cis-regulatory sequences can impact translation regulation. Additionally, RNA helicases such as DHX29 and Ded1/DDX3 may participate in the process of translation initiation, especially for mRNAs with structured 5'UTRs. The best-studied example of cap-independent translation initiation in eukaryotes is that by the Internal ribosome entry site (IRES). What differentiates cap-independent translation from cap-dependent translation is that cap-independent translation does not require the 5' cap to initiate scanning from the 5' end of the mRNA until the start codon. The ribosome can
Eukaryotic translation
11092729
Rotavirus translation Rotavirus translation, the process of translating mRNA into proteins, occurs in a different way in Rotaviruses. Unlike the vast majority of cellular proteins in other organisms, in Rotaviruses the proteins are translated from capped but nonpolyadenylated mRNAs. The viral nonstructural protein NSP3 specifically binds the 3'-end consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIF4G. The Rotavirus replication cycle occurs entirely in the cytoplasm. Upon virus entry, the viral transcriptase synthesizes capped but nonpolyadenylated mRNA The viral mRNAs bear 5' and 3' untranslated regions (UTR) of variable length and are flanked by two
Rotavirus translation
6557151
promoting subunit dissociation. Accordingly, loss of HflX results in an increase in stalled ribosomes upon heat shock and possibly other stress conditions. Several antibiotics exert their action by targeting the translation process in bacteria. They exploit the differences between prokaryotic and eukaryotic translation mechanisms to selectively inhibit protein synthesis in bacteria without affecting the host. Prokaryotic translation Prokaryotic translation is the process by which messenger RNA is translated into proteins in prokaryotes. Initiation of translation in prokaryotes involves the assembly of the components of the translation system, which are: the two ribosomal subunits (50S and 30S subunits); the mature mRNA
Prokaryotic translation
8684269
conserved double stranded RNA binding motif, dsRBM1 and dsRBM2. PKR is induced by interferon in a latent state. Binding to dsRNA is believed to activate PKR by inducing dimerization and subsequent auto-phosphorylation reactions. In situations of viral infection, the dsRNA created by viral replication and gene expression binds to the N-terminal domain, activating the protein. Once active, PKR is able to phosphorylate the eukaryotic translation initiation factor eIF2α. This inhibits further cellular mRNA translation, thereby preventing viral protein synthesis. Since ElF2α is involved in the commonly initiation translation from an AUG codon, the alternative non-AUG initiation takes place instead. An
Protein kinase R
11354082
RNA binding subunit of the eIF3 complex. EIF3D has been shown to interact with PHLDA1 and EIF3A. EIF3D Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a protein that in humans is encoded by the "EIF3D" gene. Eukaryotic translation initiation factor-3 (eIF3), the largest of the eIFs, is a multiprotein complex composed of at least ten nonidentical subunits. The complex binds to the 40S ribosome and helps maintain the 40S and 60S ribosomal subunits in a dissociated state. It is also thought to play a role in the formation of the 40S initiation complex by interacting with the ternary
EIF3D
10294305
Hepatitis A virus internal ribosome entry site (IRES) This family represents the internal ribosome entry site (IRES) of the hepatitis A virus. HAV IRES is a 450 nucleotide long sequence located in the 735 nt long 5’ UTR (untranslated region) of Hepatitis A viral RNA genome. IRES elements allow cap and end-independent translation of mRNA in the host cell. The IRES achieves this by mediating the internal initiation of translation by recruiting a ribosomal 40S pre-initiation complex directly to the initiation codon and eliminates the requirement for eukaryotic initiation factor, eIF4F. The IRES was first discovered in the RNA genome
Hepatitis A virus internal ribosome entry site (IRES)
12972445
there is a balance between the processes of translation and mRNA decay. Messages which are being actively translated are bound by polysomes and the eukaryotic initiation factors eIF-4E and eIF-4G (in eukaryotes). This blocks access to the cap by the decapping enzyme DCP2 and protects the mRNA molecule. In nutrient-starvation conditions or viral infection, translation may be compromised and decapping is stimulated. This balance is reflected in the size and abundance of the cytoplasmic structures known as P-bodies. A number of specific decay pathways exist that recognize aberrant messages and promote their decapping. Nonsense mediated decay recognizes premature stop codons
Messenger RNA decapping
8896846
Drosha Drosha is a Class 2 ribonuclease III enzyme that in humans is encoded by the "DROSHA" (formerly "RNASEN") gene. Members of the ribonuclease III superfamily of double-stranded (ds) RNA-specific endoribonucleases participate in diverse RNA maturation and decay pathways in eukaryotic and prokaryotic cells. The RNase III Drosha is the core nuclease that executes the initiation step of microRNA (miRNA) processing in the nucleus. The microRNAs thus generated are short RNA molecules that regulate a wide variety of other genes by interacting with the RNA-induced silencing complex (RISC) to induce cleavage of complementary messenger RNA (mRNA) as part of the
Drosha
4008743
interacting with mRNA at the other end; the latter pairing between the tRNA and mRNA ensures that the correct amino acid is added to the chain. Protein synthesis occurs in three phases: initiation, elongation, and termination. Prokaryotic translation differs from eukaryotic translation; however, this section will mostly focus on the commonalities between the two organisms. Before translation can begin, the process of binding a specific amino acid to its corresponding tRNA must occur. This reaction, called tRNA charging, is catalyzed by aminoacyl tRNA synthetase. A specific tRNA synthetase is responsible for recognizing and charging a particular amino acid. Furthermore, this
Biosynthesis
6200767
with the 5'cap binding protein eIF4E. Interaction between these two eukaryotic initiation factors (eIFs) of the eIF4F complex is necessary for 40S ribosomal subunit recruitment to the 5' end of mRNAs, which is further thought to occur with via mRNA 5'cap to 3' poly(A) tail loop formation. The virus may even use partially-cleaved eIF4G to aid in initiation of IRES-mediated translation. Cells may also use IRESs to increase translation of certain proteins during mitosis and programmed cell death. In mitosis, the cell dephosphorylates eIF4E so that it has little affinity for the 5'cap. As a result, the 40S ribosomal subunit
Internal ribosome entry site
15952637
female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice but no significant abnormalities were observed. EIF4E3 Eukaryotic translation initiation factor 4E family member 3 is a protein that in humans is encoded by the EIF4E3 gene. EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome. Model organisms have been used in the study of EIF4E3 function. A conditional knockout mouse line, called "Eif4e3" was generated as part of the International Knockout
EIF4E3
15952636
EIF4E3 Eukaryotic translation initiation factor 4E family member 3 is a protein that in humans is encoded by the EIF4E3 gene. EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome. Model organisms have been used in the study of EIF4E3 function. A conditional knockout mouse line, called "Eif4e3" was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and
EIF4E3
10563697
transcribed. Thus translation and transcription are parallel processes. Bacterial mRNA are usually polycistronic and contain multiple ribosome binding sites. Translation initiation is the most highly regulated step of protein synthesis in prokaryotes. The rate of translation depends on two factors: The RBS sequence affects both of these factors. The ribosomal protein S1 binds to adenine sequences upstream of the RBS. Increasing the concentration of adenine upstream of the RBS will increase the rate of ribosome recruitment. The level of complementarity of the mRNA SD sequence to the ribosomal ASD greatly affects the efficiency of translation initiation. Richer complementarity results in
Ribosome-binding site
2503442
synthesis inhibitor and a weak, non-selective, reversible monoamine oxidase inhibitor. As a protein synthesis inhibitor, linezolid stops the growth and reproduction of bacteria by disrupting translation of messenger RNA (mRNA) into proteins in bacterial ribosomes. Linezolid inhibits translation at the first step of protein synthesis, "initiation", unlike most other protein synthesis inhibitors, which inhibit "elongation". It does so by preventing the formation of the initiation complex, composed of the 30S and 50S subunits of the ribosome, tRNA, and mRNA. Linezolid binds to the 23S portion of the 50S subunit (the center of peptidyl transferase activity), close to the binding sites
Linezolid
6200763
Internal ribosome entry site An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at the 5' end of mRNA molecules, since 5' cap recognition is required for the assembly of the initiation complex. The location for IRES elements is often in the 5'UTR, but can also occur elsewhere in mRNAs. IRES sequences were first discovered in 1988 in the poliovirus (PV) and encephalomyocarditis virus (EMCV) RNA genomes in the labs of Nahum Sonenberg and
Internal ribosome entry site
10563695
Ribosome-binding site A ribosome binding site, or ribosomal binding site (RBS), is a sequence of nucleotides upstream of the start codon of an mRNA transcript that is responsible for the recruitment of a ribosome during the initiation of protein translation. Mostly, RBS refers to bacterial sequences, although internal ribosome entry sites (IRES) have been described in mRNAs of eukaryotic cells or viruses that infect eukaryotes. Ribosome recruitment in eukaryotes is generally mediated by the 5' cap present on eukaryotic mRNAs. The RBS in prokaryotes is a region upstream of the start codon. This region of the mRNA has the consensus
Ribosome-binding site
10430380
Cap binding complex The 5' cap of eukaryotic messenger RNA is bound at all times by various cap-binding complexes (CBCs). In the nucleus freshly transcribed mRNA molecules are bound on the 5' cap by the nuclear cap-binding complex of Cbc1/Cbc2 in yeast or CBP20/CBP80 in metazoans. These aid in the export of the mRNA and protect it from decapping. They also serve as a marker for the so-called pioneer round of translation when the message is examined by nonsense mediated decay. After the first round of translation ("pioneer round"), CBC20/80 is replaced by the translation initiation factor eIF4E. The eIF4F
Cap binding complex
9717328
mRNA strand near the exit site of the 40S ribosomal subunit, thus promoting the assembly of a functional pre-initiation complex. In many human cancers, eIF3 subunits are overexpressed (subunits a, b, c, h, i, and m) and underexpressed (subunits e and f). One potential mechanism to explain this disregulation comes from the finding that eIF3 binds a specific set of cell proliferation regulator mRNA transcripts and regulates their translation. eIF3 also mediates cellular signaling through S6K1 and mTOR/Raptor to effect translational regulation. The eIF4F complex is composed of three subunits: eIF4A, eIF4E, and eIF4G. Each subunit has multiple human isoforms
Eukaryotic initiation factor
773204
place during S phase of the cell cycle. Transcription is the process by which the information contained in a section of DNA is replicated in the form of a newly assembled piece of messenger RNA (mRNA). Enzymes facilitating the process include RNA polymerase and transcription factors. In eukaryotic cells the primary transcript is pre-mRNA. Pre-mRNA must be processed for translation to proceed. Processing includes the addition of a 5' cap and a poly-A tail to the pre-mRNA chain, followed by splicing. Alternative splicing occurs when appropriate, increasing the diversity of the proteins that any single mRNA can produce. The product
Central dogma of molecular biology
10294312
the IRES forms, suppressing the IRES’s ability to perform the cap-independent translation. A host cell protein found widely and exclusively in eukaryotic cells, La protein binds directly to specific regions on the HAV IRES during mRNA translation as well as RNA replication. In a 2008 study, cytoplasmic La was observed to reduce HAV IRES initiation. However, in 2014, a more recent study demonstrated successful inhibition (in vivo) of La protein as a proposed method for inhibiting the HAV IRES translation and replication, which means that it more than likely plays an integral role in the HAV translation and replication. Amantadine,
Hepatitis A virus internal ribosome entry site (IRES)
11427458
preinitiation complexes starting from the 5’ end of the mRNA. Next, induction via eIF1 and eIF1A are needed to disclose the conformation of the 40S subunit in order to induce DEAD-box RNA helicase eIF4A, its cofactor eIF4B, and eIF4G activity. EIF1 Eukaryotic translation initiation factor 1 (eIF1) is a protein that in humans is encoded by the "EIF1" gene. eIF1 interacts with the eukaryotic small (40S) ribosomal subunit and eIF3, and is a component of the 43S preinitiation complex (PIC). eIF1 and eIF1A bind cooperatively to the 40S to stabilize an "open" conformation of the preinitiation complex (PIC) during eukaryotic
EIF1
269933
multi-step biochemical reaction. In some instances, an mRNA will be edited, changing the nucleotide composition of that mRNA. An example in humans is the apolipoprotein B mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which, upon translation, produces a shorter protein. Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA (mRNA) molecules are polyadenylated at the 3' end, but recent studies have shown that short stretches of uridine (oligouridylation) are also common. The poly(A) tail and the protein bound to
Messenger RNA
20505599
the eukaryotic small ribosomal subunit (40S) and eIF3. DHX29 DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene. This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein functions in translation initiation, and is specifically required for ribosomal scanning across stable mRNA secondary structures during initiation codon selection. This protein may also play a role in sensing virally derived cytosolic nucleic acids. Knockdown of this gene results in reduced protein translation and impaired proliferation of cancer
DHX29
11427457
responsible for the investigation of codon-anticodon mismatches during the initiation of translation. In order to determine the structure of human eIF1, an experiment with N-terminal His tag and eIF1 are conducted via using NMR spectroscopy. Scientists have discovered a binding site by generating yeast mutation and study the neighbor conserved residues located in the same region. GST pull-down experiments has shown that eIF1 binds precisely to the p110 subunit of eIF3 as a result explaining eIF1 recruiting. The function of eIf1 has some hidden aspects. However, in all eukaryotic cells initiation of mRNA translation starts with scanning via ribosomal 43S
EIF1
6200771
interpreting data produced using bicistronic reporter constructs. For example, there are several known cases of mis-reported IRES elements that were later recognized as promoter-containing regions. More recently, splice acceptor sites within several presumed IRES segments have been shown to be responsible for apparent IRES function in bicistronic reporter assays. Internal ribosome entry site An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at the 5' end of mRNA molecules, since 5' cap recognition is
Internal ribosome entry site
10563700
and poly(A)-binding protein (PABP) recognize the 5' capped mRNA and recruit the 43S ribosome complex at that location. Translation initiation happens following recruitment of the ribosome, at the start codon (underlined) found within the Kozak consensus sequence ACCAUGG. Since the Kozak sequence itself is not involved in the recruitment of the ribosome, it is not considered a ribosome binding site. Eukaryotic ribosomes are known to bind to transcripts in a mechanism unlike the one involving the 5' cap, at a sequence called the internal ribosome entry site. This process is not dependent on the full set of translation initiation factors
Ribosome-binding site
19247990
reasons. The eIF3 subunits exist at equal stoichiometry within the complex, with the exception of eIF3J, which is loosely bound and non-essential for viability in several species. The subunits were originally organized alphabetically by molecular weight in mammals (A as the highest), but the arrangement of molecular weight can vary between species. Molecular weight of human subunits. Eukaryotic initiation factor 3 Eukaryotic initiation factor 3 (eIF3) is a multiprotein complex that functions during the initiation phase of eukaryotic translation. It is essential for most forms of cap-dependent and cap-independent translation initiation. In humans, eIF3 consists of 13 nonidentical subunits (eIF3a-m)
Eukaryotic initiation factor 3
11305661
EIF2S1 Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the "EIF2S1" gene. The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNA) to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article), beta (β, 38 kD), and gamma (γ, 52 kD). The rate of formation of the
EIF2S1
11305663
proper functioning of eIF2α appears essential for preventing diet-induced type II diabetes. Salubrinal is a selective inhibitor of enzymes that dephosphorylate eIF2α. Salubrinal also blocks eIF2α dephosphorylation by a herpes simplex virus protein and inhibits viral replication. eIF2α phosphorylation is cytoprotective during endoplasmic reticulum stress. EIF2S1 Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the "EIF2S1" gene. The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator
EIF2S1
269948
of nucleotides long can stimulate the degradation of specific mRNAs by base-pairing with complementary sequences and facilitating ribonuclease cleavage by RNase III. It was recently shown that bacteria also have a sort of 5' cap consisting of a triphosphate on the 5' end. Removal of two of the phosphates leaves a 5' monophosphate, causing the message to be destroyed by the exonuclease RNase J, which degrades 5' to 3'. Inside eukaryotic cells, there is a balance between the processes of translation and mRNA decay. Messages that are being actively translated are bound by ribosomes, the eukaryotic initiation factors eIF-4E and
Messenger RNA
19247984
Eukaryotic initiation factor 3 Eukaryotic initiation factor 3 (eIF3) is a multiprotein complex that functions during the initiation phase of eukaryotic translation. It is essential for most forms of cap-dependent and cap-independent translation initiation. In humans, eIF3 consists of 13 nonidentical subunits (eIF3a-m) with a combined molecular weight of ~800 kDa, making it the largest translation initiation factor. The eIF3 complex is broadly conserved across eukaryotes, but the conservation of individual subunits varies across organisms. For instance, while most mammalian eIF3 complexes are composed of 13 subunits, budding yeast's eIF3 has only six subunits (eIF3a, b, c, g, i, j).
Eukaryotic initiation factor 3
19341176
Eukaryotic initiation factor 4F Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric protein complex that binds the 5' cap of messenger RNAs (mRNAs) to promote eukaryotic translation initiation. The eIF4F complex is composed of three non-identical subunits: the DEAD-box RNA helicase eIF4A, the cap-binding protein eIF4E, and the large "scaffold" protein eIF4G. The mammalian eIF4F complex was first described in 1983, and has been a major area of study into the molecular mechanisms of cap-dependent translation initiation ever since. eIF4F is important for recruiting the small ribosomal subunit (40S) to the 5' cap of mRNAs during cap-dependent translation initiation. Components
Eukaryotic initiation factor 4F
269931
enzymes during transcription so that processing can proceed quickly after the start of transcription. The short-lived, unprocessed or partially processed product is termed "precursor mRNA", or "pre-mRNA"; once completely processed, it is termed "mature mRNA". Processing of mRNA differs greatly among eukaryotes, bacteria, and archea. Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires extensive processing. A "5' cap" (also termed an RNA cap, an RNA 7-methylguanosine cap, or an RNA mG cap) is a modified guanine nucleotide that has been added to the "front" or 5' end of
Messenger RNA
11791012
elements within the mRNA required to bind trans-acting factors, potentially affecting any step in post-transcriptional gene expression including pre-mRNA processing and splicing, transport, translation, and degradation. The splicing of mRNA can induce its translation and functionally diversify the repertoire of proteins it encodes. The Zeb2 mRNA, which has a particularly long 5’UTR, requires the retention of a 5’UTR intron that contains an internal ribosome entry site for efficient translation. However, retention of the intron is dependent on the expression of an antisense transcript that complements the intronic 5’ splice site. Therefore, the ectopic expression of the antisense transcript represses splicing
Long non-coding RNA
11196524
two exons contain upstream AUGs (uAUGs) that can potentially act as sites for translation initiation (see eukaryotic translation), affecting protein translation and SFTPA1 relative content. The majority of SFTPA1 transcripts lack exon B, a sequence implicated in transcription and translation enhancement, indicating a differential regulation of SFTPA1 and SFTPA2 expression. The AD’ form is the most represented among SFTPA1 transcripts (81%), and experimental work has shown that this sequence can stabilize mRNA and enhance translation, but the mechanisms implicated in this regulation are still under investigation. While differences at the 5’UTR are shown to regulate both transcription and translation, polymorphisms
Surfactant protein A1
11147698
all cellular mRNA require eIF4E in order to be translated into protein. The eIF4E polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. The other subunits of eIF4F are a 47-kD polypeptide, termed eIF4A, that possesses ATPase and RNA helicase activities, and a 220-kD scaffolding polypeptide, eIF4G. Some viruses cut eIF4G in such a way that the eIF4E binding site is removed and the virus is able to translate its proteins without eIF4E. Also some cellular proteins, the most notable being heat shock proteins, do not require
EIF4E
12691930
EIF4A The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA. The mechanisms governing the basic subsistence of eukaryotic cells are immensely complex; it is therefore unsurprising that regulation occurs at a number of stages of protein synthesis – the regulation of translation has become a well-studied field. Human translational control is of increasing research interest as it has connotations in a range of diseases. Orthologs of many of
EIF4A
12691922
EIF4A The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA. The mechanisms governing the basic subsistence of eukaryotic cells are immensely complex; it is therefore unsurprising that regulation occurs at a number of stages of protein synthesis – the regulation of translation has become a well-studied field. Human translational control is of increasing research interest as it has connotations in a range of diseases. Orthologs of many of
EIF4A
6066113
is no longer infectious whereas poliovirus retains infectivity even with the absence of VPg. Because VPg sits at the 5' end of the genome, similar to eukaryotic 5' mRNA caps, several experiments were performed to explore its function in translation. Poliovirus utilizes an internal ribosome entry site (IRES) instead of a cap for translation initiation, abrogating the requirement of VPg in initial infection whereas studies with feline calicivirus confirmed that the VPg protein interacts directly with the cap-binding protein of the ribosome, eIF4E, and that this interaction is essential for viral translation. "Principles of Virology" by S.J. Flint, L.W. Enquist,
VPg
19341179
an important target of mTOR signaling through the eIF4E binding protein (4E-BP). Phosphorylation of 4E-BPs by mTOR prevents their binding to eIF4E, freeing eIF4E to bind eIF4G and participate in translation initiation. Eukaryotic initiation factor 4F Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric protein complex that binds the 5' cap of messenger RNAs (mRNAs) to promote eukaryotic translation initiation. The eIF4F complex is composed of three non-identical subunits: the DEAD-box RNA helicase eIF4A, the cap-binding protein eIF4E, and the large "scaffold" protein eIF4G. The mammalian eIF4F complex was first described in 1983, and has been a major area of
Eukaryotic initiation factor 4F
4904567
germ line DNA by homologous recombinational repair. There are a lot of mRNAs that have been transcribed but not translated during dictyate. Shortly before ovulation, the oocyte of interest activates these mRNA strains. Translation of mRNA in dictyate is partly explained by molecules binding to sites on the mRNA strain, which results in that initiation factors of translation can not bind to that site. Two such molecules, that impedes initiation factors, are CPEB and "maskin", which bind to CPE (cytoplasmic polyadenylation element). When these two molecules remain together, then maskin binds the initiation factor eIF-4E, and thus eIF4E can no
Dictyate
13759942
surround the GCC initiation codon and are known as SL1 to SL3. Mutations that disrupted these stem-loop structures showed that SL1 and SL2 as required for translation initiation from the GGC codon but SL3 has no effect on translation efficiency. Translation initiation from the GGC codon was shown to be is mediated by an internal ribosome entry site (IRES) which requires SL1 located upstream of the IRES and SL2 located downstream. This study also showed that SL3 influences the choice of downstream AUG translation initiation codons that will produce the normal 50-KDa human ACAT1 protein. ACAT1 mRNA Human acetyl-coA cholesterol
ACAT1 mRNA
6557183
eIF3 also interacts with the eIF4F complex, which consists of three other initiation factors: eIF4A, eIF4E, and eIF4G. eIF4G is a scaffolding protein that directly associates with both eIF3 and the other two components. eIF4E is the cap-binding protein. Binding of the cap by eIF4E is often considered the rate-limiting step of cap-dependent initiation, and the concentration of eIF4E is a regulatory nexus of translational control. Certain viruses cleave a portion of eIF4G that binds eIF4E, thus preventing cap-dependent translation to hijack the host machinery in favor of the viral (cap-independent) messages. eIF4A is an ATP-dependent RNA helicase that aids
Eukaryotic translation
2219863
contains binding sites for poly(A) binding proteins (PABPs). These proteins cooperate with other factors to affect the export, stability, decay, and translation of an mRNA. PABPs bound to the poly(A) tail may also interact with proteins, such as translation initiation factors, that are bound to the 5' cap of the mRNA. This interaction causes circularization of the transcript, which subsequently promotes translation initiation. Furthermore, it allows for efficient translation by causing recycling of ribosomes. While the presence of a poly(A) tail usually aids in triggering translation, the absence or removal of one often leads to exonuclease-mediated degradation of the mRNA.
Three prime untranslated region
12182791
Protein synthesis inhibitor A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used to describe nearly any antibiotic, in practice, it usually refers to substances that act at the ribosome level (either the ribosome itself or the translation factor), taking advantages of the major differences between prokaryotic and eukaryotic ribosome structures. In general, protein synthesis inhibitors work at different stages of prokaryotic mRNA translation into proteins, like initiation, elongation (including
Protein synthesis inhibitor
12547304
EIF2 Eukaryotic Initiation Factor 2 (eIF2) is a eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNA to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer consisting of an alpha (also called subunit 1), a beta (subunit 2), and a gamma (subunit 3) subunit. Once the initiation phase has completed, eIF2 is released from the ribosome bound to GDP as an inactive binary complex. To participate in another round of translation initiation, this GDP must be exchanged for GTP. eIF2 is an essential factor for protein synthesis that
EIF2
11153157
EIF4G2 Eukaryotic translation initiation factor 4 gamma 2 (also called p97, NAT1, and DAP-5) is a protein that in humans is encoded by the "EIF4G2" gene. Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by the eIF4G2 gene shares similarity with the C-terminal region of eIF4G1 that contains the binding sites for eIF4A and eIF3. eIF4G2 additionally contains a binding site for eIF4E at the N-terminus. Unlike eIF4G1, which supports cap-dependent
EIF4G2
269938
be processed or transported, translation by the ribosome can begin immediately after the end of transcription. Therefore, it can be said that prokaryotic translation is "coupled" to transcription and occurs "co-transcriptionally". Eukaryotic mRNA that has been processed and transported to the cytoplasm (i.e., mature mRNA) can then be translated by the ribosome. Translation may occur at ribosomes free-floating in the cytoplasm, or directed to the endoplasmic reticulum by the signal recognition particle. Therefore, unlike in prokaryotes, eukaryotic translation "is not" directly coupled to transcription. It is even possible in some contexts that reduced mRNA levels are accompanied by increased protein
Messenger RNA
4296528
pairing with the 3'-terminus of 16S rRNA might serve to abort peptide bond formation after out-of-phase initiation. Mutations in the Shine-Dalgarno sequence can reduce or increase translation in prokaryotes. This change is due to a reduced or increased mRNA-ribosome pairing efficiency, as evidenced by the fact that compensatory mutations in the 3'-terminal 16S rRNA sequence can restore translation. Shine-Dalgarno sequence The Shine-Dalgarno (SD) Sequence is a ribosomal binding site in bacterial and archaeal messenger RNA, generally located around 8 bases upstream of the start codon AUG. The RNA sequence helps recruit the ribosome to the messenger RNA (mRNA) to initiate
Shine-Dalgarno sequence
10121528
mRNA with the subunits of ribosomal complexes. These naturally occurring regulatory molecules, or binding proteins (BPs), bind to eukaryotic initiation factor eIF4E, preventing its association with eIF4G, another initiation factor. These two proteins, under unregulated conditions, form a complex, known as eIF4F, which associates with the 5’ cap of mRNA and the ribosomal subunits. eIF4E BPs (4E-BPs), as small polypeptides, consist of the same amino acid sequence as the portion of eIF4G that interacts with eIF4E. 4EGI-1 thus prevents the proper association of mRNA, carrying the coded message of transcribed genes, with the ribosome, the cellular component necessary for the
4EGI-1
11398942
and SUI1 domains and these domains may function in RNA binding and translation initiation, respectively. LGTN Ligatin, otherwise known as eIF2D, is a protein that in humans is encoded by the "LGTN" gene. This protein is not a component of the heterotrimeric eIF2 complex, but instead functions in different pathways of eukaryotic translation. This gene encodes a protein receptor that localizes phosphoglycoproteins within endosomes and at the cell periphery. This trafficking receptor for phosphoglycoproteins may play a role in neuroplasticity by modulating cell-cell interactions, intracellular adhesion, and protein binding at membrane surfaces. In hippocampal neurons, long-lasting down-regulation of ligatin mRNA
LGTN
7359972
Kozak consensus sequence The Kozak consensus sequence, Kozak consensus or Kozak sequence is a sequence which occurs on eukaryotic mRNA and has the consensus (gcc)gccRccAUGG. The Kozak consensus sequence plays a major role in the initiation of the translation process. The sequence was named after the scientist who discovered it, Marilyn Kozak. The sequence is identified by the notation (gcc)gccRccAUGG, which summarizes data analysed by Kozak from a wide variety of sources (about 699 in all) as follows: Kozak's paper was limited to a subset of vertebrates ("i.e." human, cow, cat, dog, chicken, guinea pig, hamster, mouse, pig, rabbit, sheep,
Kozak consensus sequence
14505309
cytoskeleton-related proteins MAP2 and Arc. Researchers provided evidence of local synthesis, by examining the distribution of Arc mRNA after selective stimulation of certain synapses of a hippocampal cell. They found that Arc mRNA was localized at the activated synapses, and Arc protein appeared there simultaneously. This suggests that the mRNA was translated locally. These mRNA transcripts are translated in a cap-dependent manner, meaning they use a "cap" anchoring point to facilitate ribosome attachment to the 5' untranslated region. Eukaryotic initiation factor 4 group (eIF4) members recruit ribosomal subunits to the mRNA terminus, and assembly of the eIF4F initiation complex is
Synaptic tagging
10121533
of weak mRNA’s. Cap-dependent translation involves a series of steps that join the small and large ribosomal subunits at the start codon of mRNA. The initiation factor complex eIF4F is dependent upon the presence of a 5’ mRNA cap upstream from the start codon in order to initiate translation. Initiation factor independent translation does not require the association of initiation factors with the 5’ cap of mRNA. As an alternative, the associated ribosomal units are moved to the start location by internal ribosome entry site trans acting factors (ITAFs). It has been found that several cellular proteins that respond to
4EGI-1
19247986
initiation factors, the auxiliary factor DHX29, and mRNA. eIF3 is a component of the multifactor complex (MFC) and 43S and 48S preinitiation complexes (PICs). The interactions of eIF3 with other initiation factors can vary amongst species; for example, mammalian eIF3 directly interacts with the eIF4F complex (via eIF4G), while budding yeast lacks this connection. However, both mammalian and yeast eIF3 independently bind eIF1, eIF4B, and eIF5. Several subunits of eIF3 contain RNA recognition motifs (RRMs) and other RNA binding domains to form a multisubunit RNA binding interface through which eIF3 interacts with cellular and viral IRES mRNA, including the HCV
Eukaryotic initiation factor 3
11427456
EIF1 Eukaryotic translation initiation factor 1 (eIF1) is a protein that in humans is encoded by the "EIF1" gene. eIF1 interacts with the eukaryotic small (40S) ribosomal subunit and eIF3, and is a component of the 43S preinitiation complex (PIC). eIF1 and eIF1A bind cooperatively to the 40S to stabilize an "open" conformation of the preinitiation complex (PIC) during eukaryotic translation initiation. eIF1 binds to a region near the ribosomal A-site in the 40S subunit and functions in a manner similar to the structurally related bacterial counterpart IF1. eIF1 is a conserved translation protein in all eukaryotic cells that is
EIF1