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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 a sequence like such 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. ^ a b Jacks T, Madhani HD, Masiarz FR, Varmus HE (November 1988). "Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region". Cell. 55 (3): 447–458. doi:10.1016/0092-8674(88)90031-1. PMID 2846182.
  2. ^ Green L, Kim CH, Bustamante C, Tinoco I Jr. "Characterization of the Mechanical Unfolding of RNA Pseudoknots." J Mol Biol. 26 May 2007
  3. ^ Chien-Hung Yu, Mathieu H. M. Noteborn and René C. L. Olsthoorn.Stimulation of ribosomal frameshifting by antisense LNA. Nucl.Acids Res (2010) 38 (22):8277–8238
  4. ^ "Archived copy". Archived from the original on 2013-10-02. Retrieved 2013-07-28.{{cite web}}: CS1 maint: archived copy as title (link)
  5. ^ "Molecular Biology: Frameshifting occurs at slippery sequences". Molecularstudy.blogspot.com. Retrieved 2013-07-28.
  6. ^ Farabaugh, P. J.; Björk, G. R. (15 March 1999). "How translational accuracy influences reading frame maintenance". EMBO J. 18 (6): 1427–1434. doi:10.1093/emboj/18.6.1427. PMC 1171232. PMID 10075915.
  7. ^ Cao, S; Chen, SJ (11 March 2008). "Predicting ribosomal frameshifting efficiency". Physical biology. 5 (1): 016002. doi:10.1088/1478-3975/5/1/016002. PMC 2442619. PMID 18367782.{{cite journal}}: CS1 maint: article number as page number (link)
  8. ^ a b Lin, Z; Gilbert, RJ; Brierley, I (1 September 2012). "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. doi:10.1093/nar/gks629. PMID 22743270.
  9. ^ Huang, Xiaolan; Cheng, Qiang; Du, Zhihua (2013). "A Genome-Wide Analysis of RNA Pseudoknots That Stimulate Efficient −1 Ribosomal Frameshifting or Readthrough in Animal Viruses". BioMed Research International. 2013: 1–15. doi:10.1155/2013/984028.