Slippery sequence

File:Tandem_slippage_model.jpg, 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).{{cite journal | vauthors = Jacks T, Madhani HD, Masiarz FR, Varmus HE | title = Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region | journal = Cell | volume = 55 | issue = 3 | pages = 447–58 | date = November 1988 | pmid = 2846182 | doi = 10.1016/0092-8674(88)90031-1 | pmc = 7133365 | s2cid = 25672863 }} ]]

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.{{cite journal | vauthors = Green L, Kim CH, Bustamante C, Tinoco I | title = Characterization of the mechanical unfolding of RNA pseudoknots | journal = Journal of Molecular Biology | volume = 375 | issue = 2 | pages = 511–28 | date = January 2008 | pmid = 18021801 | doi = 10.1016/j.jmb.2007.05.058 | pmc = 7094456 }}{{cite journal | vauthors = Yu CH, Noteborn MH, Olsthoorn RC | title = Stimulation of ribosomal frameshifting by antisense LNA | journal = Nucleic Acids Research | volume = 38 | issue = 22 | pages = 8277–83 | date = December 2010 | pmid = 20693527 | pmc = 3001050 | doi = 10.1093/nar/gkq650 }}{{cite web |url=http://www.path.cam.ac.uk/research/investigators/brierley/research.html |title=Dr Ian Brierley Research description | work = Department of Pathology, University of Cambridge |access-date=2013-07-28 |url-status=dead |archive-url=https://web.archive.org/web/20131002121121/http://www.path.cam.ac.uk/research/investigators/brierley/research.html |archive-date=2013-10-02 }}{{cite web |url= http://molecularstudy.blogspot.com/2012/10/frameshifting-occurs-at-slippery.html |title=Molecular Biology: Frameshifting occurs at slippery sequences |publisher=Molecularstudy.blogspot.com |date= 2012-10-16|access-date=2013-07-28}}{{cite journal | vauthors = Farabaugh PJ, Björk GR | title = How translational accuracy influences reading frame maintenance | journal = The EMBO Journal | volume = 18 | issue = 6 | pages = 1427–34 | date = March 1999 | pmid = 10075915 | pmc = 1171232 | doi = 10.1093/emboj/18.6.1427 }} 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.

The frameshift occurs due to wobble pairing. The Gibbs free energy of secondary structures downstream give a hint at how often frameshift happens.{{cite journal | vauthors = Cao S, Chen SJ | title = Predicting ribosomal frameshifting efficiency | journal = Physical Biology | volume = 5 | issue = 1 | pages = 016002 | date = March 2008 | pmid = 18367782 | pmc = 2442619 | doi = 10.1088/1478-3975/5/1/016002 | bibcode = 2008PhBio...5a6002C }} Tension on the mRNA molecule also plays a role. A list of slippery sequences found in animal viruses is available from Huang et al.{{cite journal | vauthors = Huang X, Cheng Q, Du Z | title = A genome-wide analysis of RNA pseudoknots that stimulate efficient -1 ribosomal frameshifting or readthrough in animal viruses | journal = BioMed Research International | volume = 2013 | pages = 984028 | date = 2013 | pmid = 24298557 | pmc = 3835772 | doi = 10.1155/2013/984028 | doi-access = free }}

Slippery sequences that cause a 2-base slip (−2 frameshift) have been constructed out of the HIV UUUUUUA sequence.{{cite journal | vauthors = Lin Z, Gilbert RJ, Brierley I | title = Spacer-length dependence of programmed -1 or -2 ribosomal frameshifting on a U6A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting | journal = Nucleic Acids Research | volume = 40 | issue = 17 | pages = 8674–89 | date = September 2012 | pmid = 22743270 | pmc = 3458567 | doi = 10.1093/nar/gks629 | doi-access = free }}