The signal recognition particle RNA, (also known as 7SL, 6S, ffs, or 4.5S RNA) is part of the signal recognition particle (SRP) ribonucleoprotein complex. SRP recognizes the signal peptide and binds to the ribosome, halting protein synthesis. SRP-receptor is a protein that is embedded in a membrane, and which contains a transmembrane pore. When the SRP-ribosome complex binds to SRP-receptor, SRP releases the ribosome and drifts away. The ribosome resumes protein synthesis, but now the protein is moving through the SRP-receptor transmembrane pore. In this way SRP directs the movement of proteins within the cell to bind with a transmembrane pore which allows the protein to cross the membrane to where it is needed. The RNA and protein components of this complex are highly conserved but do vary between the different kingdoms of life. The common SINE family Alu probably originated from a 7SL RNA gene after deletion of a central sequence. The eukaryotic SRP consists of a 300-nucleotide 7S RNA and six proteins: SRPs 72, 68, 54, 19, 14, and 9. Archaeal SRP consists of a 7S RNA and homologues of the eukaryotic SRP19 and SRP54 proteins. Eukaryotic and archaeal 7S RNAs have very similar secondary structures. In most bacteria, the SRP consists of an RNA molecule (4.5S) and the Ffh protein (a homologue of the eukaryotic SRP54 protein). Some Gram-positive bacteria (e.g. Bacillus subtilis) have a longer eukaryote-like SRP RNA that includes an Alu domain. In eukaryotes and archaea, eight helical elements fold into the Alu and S domains, separated by a long linker region. The Alu domain is thought to mediate the peptide chain elongation retardation function of the SRP. The universally conserved helix which interacts with the SRP54 M domain mediates signal sequence recognition. The SRP19-helix 6 complex is thought to be involved in SRP assembly and stabilises helix 8 for SRP54. binding Humans have three functional SRP RNA genes, conveniently named RN7SL1, RN7SL2, and RN7SL3. The human genome in particular is known to contain a large amount of SRP RNA related sequence, including Alu repeats.
Discovery SRP RNA was first detected in avian and murine oncogenic RNA (ocorna) virus particles. Subsequently, SRP RNA was found to be a stable component of uninfected HeLa cells where it associated with membrane and polysome fractions. In 1980, cell biologists purified from canine pancreas an 11S "signal recognition protein" (fortuitously also abbreviated "SRP") which promoted the translocation of secretory proteins across the 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). In Archaea, SRP delivers proteins to the plasma membrane. In the bacteria, SRP primarily incorporates proteins into the inner membrane.
Post-translational transport SRP participates also in the sorting of proteins after their synthesis has been completed (post-translational protein sorting). In eukaryotes, tail-anchored proteins possessing a hydrophobic insertion sequence at their C-terminus are delivered to the endoplasmic reticulum (ER) by the SRP. Similarly, the SRP assists post-translationally in the import of nuclear-encoded proteins to the thylakoid membrane of chloroplasts.
Structure
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