Biology:Slippery sequence

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Tandem slippage of 2 tRNAs at rous sarcoma virus slippery sequence. After the frameshift, new base pairings are correct at the first and second nucleotides but incorrect at wobble position. E, P, and A sites of the ribosome are indicated. Location of growing polypeptide chain is not indicated in image because there is not yet consensus on whether the −1 slip occurs before or after polypeptide is transferred from P-site tRNA to A-site tRNA (in this case from the Asn tRNA to the Leu tRNA).[1]

A slippery sequence is a small section of codon nucleotide sequences (usually UUUAAAC) that controls the rate and chance of ribosomal frameshifting. A slippery sequence causes a faster ribosomal transfer which in turn can cause the reading ribosome to "slip." This allows a tRNA to shift by 1 base (−1) after it has paired with its anticodon, changing the reading frame.[2][3][4][5][6] A −1 frameshift triggered by such a sequence is a Programmed −1 Ribosomal Frameshift. It is followed by a spacer region, and an RNA secondary structure. Such sequences are common in virus polyproteins.[1]

The frameshift occurs due to wobble pairing. The Gibbs free energy of secondary structures downstream give a hint at how often frameshift happens.[7] Tension on the mRNA molecule also plays a role.[8] A list of slippery sequences found in animal viruses is available from Huang et al.[9]

Slippery sequences that cause a 2-base slip (−2 frameshift) have been constructed out of the HIV UUUUUUA sequence.[8]

See also

References

  1. 1.0 1.1 "Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region". Cell 55 (3): 447–58. November 1988. doi:10.1016/0092-8674(88)90031-1. PMID 2846182. 
  2. "Characterization of the mechanical unfolding of RNA pseudoknots". Journal of Molecular Biology 375 (2): 511–28. January 2008. doi:10.1016/j.jmb.2007.05.058. PMID 18021801. 
  3. "Stimulation of ribosomal frameshifting by antisense LNA". Nucleic Acids Research 38 (22): 8277–83. December 2010. doi:10.1093/nar/gkq650. PMID 20693527. 
  4. "Dr Ian Brierley Research description". Department of Pathology, University of Cambridge. http://www.path.cam.ac.uk/research/investigators/brierley/research.html. 
  5. "Molecular Biology: Frameshifting occurs at slippery sequences". Molecularstudy.blogspot.com. 2012-10-16. http://molecularstudy.blogspot.com/2012/10/frameshifting-occurs-at-slippery.html. 
  6. "How translational accuracy influences reading frame maintenance". The EMBO Journal 18 (6): 1427–34. March 1999. doi:10.1093/emboj/18.6.1427. PMID 10075915. 
  7. "Predicting ribosomal frameshifting efficiency". Physical Biology 5 (1): 016002. March 2008. doi:10.1088/1478-3975/5/1/016002. PMID 18367782. Bibcode2008PhBio...5a6002C. 
  8. 8.0 8.1 "Spacer-length dependence of programmed -1 or -2 ribosomal frameshifting on a U6A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting". Nucleic Acids Research 40 (17): 8674–89. September 2012. doi:10.1093/nar/gks629. PMID 22743270. 
  9. "A genome-wide analysis of RNA pseudoknots that stimulate efficient -1 ribosomal frameshifting or readthrough in animal viruses". BioMed Research International 2013: 984028. 2013. doi:10.1155/2013/984028. PMID 24298557. 

External links