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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.
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.
Keyword(s): HIV; DNA; Complementary; Frameshift mutation function; Frameshifting; Ribosomal; Ribosomes RNA-directed DNA polymerase; RNA; Massively-parallel genome sequencing
Publication Date:
2017
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: University College Cork
Funder(s): Science Foundation Ireland
Citation(s): 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
Publisher(s): Oxford University Press
File Format(s): application/pdf
Related Link(s): https://academic.oup.com/nar/article/45/17/10156/4064207/Specific-reverse-transcriptase-slippage-at-the-HIV
First Indexed: 2017-10-19 06:37:51 Last Updated: 2017-10-19 06:37:51