Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis

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dc.contributor.author Penno, Christophe
dc.contributor.author Kumari, Romika
dc.contributor.author Baranov, Pavel V.
dc.contributor.author van Sinderen, Douwe
dc.contributor.author Atkins, John F.
dc.date.accessioned 2017-10-18T09:40:13Z
dc.date.available 2017-10-18T09:40:13Z
dc.date.issued 2017
dc.identifier.citation Penno, C., Kumari, R., Baranov, P. V., van Sinderen, D. and Atkins, J. F. (2017) 'Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis', Nucleic Acids Research, 45(17), pp. 10156-10167. doi: 10.1093/nar/gkx690 en
dc.identifier.volume 45
dc.identifier.issued 17
dc.identifier.startpage 10156
dc.identifier.endpage 10167
dc.identifier.issn 0305-1048
dc.identifier.issn 1362-4962
dc.identifier.uri http://hdl.handle.net/10468/4889
dc.identifier.doi 10.1093/nar/gkx690
dc.description.abstract Synthesis of HIV GagPol involves a proportion of ribosomes translating a U6A shift site at the distal end of the gag gene performing a programmed -1 ribosomal frameshift event to enter the overlapping pol gene. In vitro studies here show that at the same shift motif HIV reverse transcriptase generates -1 and +1 indels with their ratio being sensitive to the relative concentration ratio of dNTPs specified by the RNA template slippage-prone sequence and its 5′ adjacent base. The GGG sequence 3′ adjacent to the U6A shift/slippage site, which is important for ribosomal frameshifting, is shown here to limit reverse transcriptase base substitution and indel ‘errors’ in the run of A’s in the product. The indels characterized here have either 1 more or less A, than the corresponding number of template U’s. cDNA with 5 A’s may yield novel Gag product(s), while cDNA with an extra base, 7 A’s, may only be a minor contributor to GagPol polyprotein. Synthesis of a proportion of non-ribosomal frameshift derived GagPol would be relevant in efforts to identify therapeutically useful compounds that perturb the ratio of GagPol to Gag, and pertinent to the extent in which specific polymerase slippage is utilized in gene expression. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Oxford University Press en
dc.relation.uri https://academic.oup.com/nar/article/45/17/10156/4064207/Specific-reverse-transcriptase-slippage-at-the-HIV
dc.rights © 2017, the Authors. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. en
dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
dc.subject HIV en
dc.subject DNA en
dc.subject Complementary en
dc.subject Frameshift mutation function en
dc.subject Frameshifting en
dc.subject Ribosomal en
dc.subject Ribosomes RNA-directed DNA polymerase en
dc.subject RNA en
dc.subject Massively-parallel genome sequencing en
dc.title Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork , Cork, Ireland. +353-21-490-3000. Email: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 431799819
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Irish Research Council
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nucleic Acids Research en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IP/1492/IE/Using ribosome profiling to study translation initiation/elongation and facilitate optimization of protein synthesis/
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1853/IE/Dynamic redefinition of codons: From antivirals to an essential micronutrient/
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1335/IE/Development of computational resources for the analysis of Genome Wide Information on Protein Synthesis (GWIPS)./
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/


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© 2017, the Authors. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as © 2017, the Authors. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
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