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

Penno, Christophe; Kumari, Romika; Baranov, Pavel V.; van Sinderen, Douwe; Atkins, John F.

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

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.contributor.funder	Science Foundation Ireland
dc.contributor.funder	Irish Research Council
dc.date.accessioned	2017-10-18T09:40:13Z
dc.date.available	2017-10-18T09:40:13Z
dc.date.issued	2017
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.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
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.doi	10.1093/nar/gkx690
dc.identifier.endpage	10167
dc.identifier.issn	0305-1048
dc.identifier.issn	1362-4962
dc.identifier.issued	17
dc.identifier.journaltitle	Nucleic Acids Research	en
dc.identifier.startpage	10156
dc.identifier.uri	https://hdl.handle.net/10468/4889
dc.identifier.volume	45
dc.language.iso	en	en
dc.publisher	Oxford University Press	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/
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