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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Penno C,Kumari R,Baranov PV,van Sinderen D,Atkins JF

doi

10.1093/nar/gkx690

subject

Has Abstract

pub_date

2017-09-29 00:00:00

pages

10156-10167

issue

17

eissn

0305-1048

issn

1362-4962

pii

4064207

journal_volume

45

pub_type

杂志文章

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