Slippery sequence

[[File:Tandem_slippage_model.jpg|thumb|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).<ref name=":6">{{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 }}</ref> ]] 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.<ref name="pmid18021801">{{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 }}</ref><ref name="pmid20693527">{{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 }}</ref><ref>{{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 }}</ref><ref>{{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}}</ref><ref>{{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 }}</ref> 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.<ref name=":6" />

The frameshift occurs due to wobble pairing. The Gibbs free energy of secondary structures downstream give a hint at how often frameshift happens.<ref>{{cite journal | vauthors = Cao S, Chen SJ | title = Predicting ribosomal frameshifting efficiency | journal = Physical Biology | volume = 5 | issue = 1 | article-number = 016002 | date = March 2008 | pmid = 18367782 | pmc = 2442619 | doi = 10.1088/1478-3975/5/1/016002 | bibcode = 2008PhBio...5a6002C }}</ref> Tension on the mRNA molecule also plays a role.<ref name="pmid22743270" /> A list of slippery sequences found in animal viruses is available from Huang et al.<ref>{{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 | article-number = 984028 | date = 2013 | pmid = 24298557 | pmc = 3835772 | doi = 10.1155/2013/984028 | doi-access = free }}</ref>

Slippery sequences that cause a 2-base slip (−2 frameshift) have been constructed out of the HIV UUUUUUA sequence.<ref name="pmid22743270">{{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 }}</ref>

== References == {{Reflist|32em}}

== External links == * [http://www.ekevanbatenburg.nl/PKBASE/ Pseudobase] * [http://recode.ucc.ie Recode] * {{MeshName|Frameshifting,+Ribosomal}} * [http://www.ebi.ac.uk/Tools/Wise2/index.htm Wise2] - aligns a protein against a DNA sequence allowing frameshifts and introns * [http://fasta.bioch.virginia.edu/fasta_www2/fasta_www.cgi?rm=select&pgm=fy FastY] - compare a DNA sequence to a protein sequence database, allowing gaps and frameshifts * [http://bioinfo.lifl.fr/path/ Path] {{Webarchive|url=https://web.archive.org/web/20110719124547/http://bioinfo.lifl.fr/path/ |date=2011-07-19 }} - tool that compares two frameshift proteins (back-translation principle) * [http://recode.ucc.ie Recode2] - Database of recoded genes, including those that require programmed Translational frameshift. *{{Rfam|id=RF00507|name=Coronavirus frameshifting stimulation element}}

Category:RNA Category:Gene expression Category:Cis-regulatory RNA elements Category:Coronaviridae