membrane of the endoplasmic reticulum. It was then discovered that SRP contained an RNA component. Comparing the SRP RNA genes from different species revealed helix 8 of the SRP RNA to be highly conserved in all domains of life. The regions near the 5′- and 3′-ends of the mammalian SRP RNA are similar to the dominant Alu family of middle repetitive sequences of the human genome. It is now understood that Alu DNA originated from SRP RNA by excision of the central SRP RNA-specific (S) fragment, followed by reverse transcription and integration into multiple sites of the human chromosomes. SRP RNAs have been identified also in some organelles, for example in the plastid SRPs of many photosynthetic organisms, and in the nuclear ribosomal internal transcribed spacer region of several ectomycorrhizal fungi. Transcription and processing Eukaryotic SRP RNAs are transcribed from DNA by RNA polymerase III (Pol III). RNA polymerase III also transcribes the genes for 5S ribosomal RNA, tRNA, 7SK RNA, and U6 spliceosomal RNA. The promoters of the human SRP RNA genes include elements located downstream of the transcriptional start site. Plant SRP RNA promoters contain an upstream stimulatory element (USE) and a TATA box. Yeast SRP RNA genes have a TATA box and additional intragenic promoter sequences (referred to as A- and B-blocks) which play a role in regulating transcription of the SRP gene by Pol III. In the bacteria, genes are organized in operons and transcribed by RNA polymerase. The 5′-end of the small (4.5S) SRP RNA of many bacteria is cleaved by RNase P. The ends of the Bacillus subtilis SRP RNA are processed by RNase III. So far, no SRP RNA introns have been observed. Function Co-translational translocation The SRP RNA is an integral part of the small and the large domain of the SRP. The function of the small domain is to delay protein translation until the ribosome-bound SRP has an opportunity to associate with the membrane-resident SRP receptor (SR). Within the large domain, the SRP RNA of the signal peptide-charged SRP promotes the hydrolysis of two guanosine triphosphate (GTP) molecules. This reaction releases the SRP from the SRP receptor and the ribosome, allowing translation to continue and the protein to enter the translocon. The protein transverses the membrane co-translationally (during translation) and enters into another cellular compartment or the extracellular space. In eukaryotes, the target is the membrane of the endoplasmic reticulum (ER).