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]

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  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): 447–58. doi:10.1016/0092-8674(88)90031-1. PMC 7133365. PMID 2846182. S2CID 25672863.
  2. ^ Green L, Kim CH, Bustamante C, Tinoco I (January 2008). "Characterization of the mechanical unfolding of RNA pseudoknots". Journal of Molecular Biology. 375 (2): 511–28. doi:10.1016/j.jmb.2007.05.058. PMC 7094456. PMID 18021801.
  3. ^ Yu CH, Noteborn MH, Olsthoorn RC (December 2010). "Stimulation of ribosomal frameshifting by antisense LNA". Nucleic Acids Research. 38 (22): 8277–83. doi:10.1093/nar/gkq650. PMC 3001050. PMID 20693527.
  4. ^ "Dr Ian Brierley Research description". Department of Pathology, University of Cambridge. Archived from the original on 2013-10-02. Retrieved 2013-07-28.
  5. ^ "Molecular Biology: Frameshifting occurs at slippery sequences". 2012-10-16. Retrieved 2013-07-28.
  6. ^ Farabaugh PJ, Björk GR (March 1999). "How translational accuracy influences reading frame maintenance". The EMBO Journal. 18 (6): 1427–34. doi:10.1093/emboj/18.6.1427. PMC 1171232. PMID 10075915.
  7. ^ Cao S, Chen SJ (March 2008). "Predicting ribosomal frameshifting efficiency". Physical Biology. 5 (1): 016002. Bibcode:2008PhBio...5a6002C. doi:10.1088/1478-3975/5/1/016002. PMC 2442619. PMID 18367782.
  8. ^ a b Lin Z, Gilbert RJ, Brierley I (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. PMC 3458567. PMID 22743270.
  9. ^ Huang X, Cheng Q, Du Z (2013). "A genome-wide analysis of RNA pseudoknots that stimulate efficient -1 ribosomal frameshifting or readthrough in animal viruses". BioMed Research International. 2013: 984028. doi:10.1155/2013/984028. PMC 3835772. PMID 24298557.

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