The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of translation of a transcript by differing mechanisms in viruses, prokaryotes and eukaryotes. While called untranslated, the 5′ UTR or a portion of it is sometimes translated into a protein product. This product can then regulate the translation of the main coding sequence of the mRNA. In many organisms, however, the 5′ UTR is completely untranslated, instead forming a complex secondary structure to regulate translation. The 5′ UTR has been found to interact with proteins relating to metabolism, and within the 5′ UTR. In addition, this region has been involved in transcription regulation, such as the sex-lethal gene in Drosophila. Regulatory elements within 5′ UTRs have also been linked to mRNA export. General structure Length The 5′ UTR begins at the transcription start site and ends one nucleotide (nt) before the initiation sequence (usually AUG) of the coding region. In prokaryotes, the length of the 5′ UTR tends to be 3–10 nucleotides long, while in eukaryotes it tends to be anywhere from 100 to several thousand nucleotides long. For example, the ste11 transcript in Schizosaccharomyces pombe has a 2273 nucleotide 5′ UTR while the lac operon in Escherichia coli only has seven nucleotides in its 5′ UTR. The differing sizes are likely due to the complexity of the eukaryotic regulation which the 5′ UTR holds as well as the larger pre-initiation complex that must form to begin translation. The 5′ UTR can also be completely missing, in the case of leaderless mRNAs. Ribosomes of all three domains of life accept and translate such mRNAs. Such sequences are naturally found in all three domains of life. Humans have many pressure-related genes under a 2–3 nucleotide leader. Mammals also have other types of ultra-short leaders like the TISU sequence. Elements The elements of a eukaryotic and prokaryotic 5′ UTR differ greatly. The prokaryotic 5′ UTR contains a ribosome binding site (RBS), also known as the Shine–Dalgarno sequence (AGGAGGU), which is usually 3–10 base pairs upstream from the initiation codon. In contrast, the eukaryotic 5′ UTR contains the Kozak consensus sequence (ACCAUGG), which contains the initiation codon. The eukaryotic 5′ UTR also contains cis-acting regulatory elements called upstream open reading frames (uORFs) and upstream