RNA Secondary Structure Switching during DNA Synthesis Catalyzed by HIV-1 Reverse Transcriptase†

Biochemistry ◽  
1997 ◽  
Vol 36 (48) ◽  
pp. 14778-14785 ◽  
Author(s):  
Zucai Suo ◽  
Kenneth A. Johnson
Keyword(s):  
Secondary Structure ◽  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Rna Secondary Structure ◽  
Structure Switching ◽  
Hiv 1

scholarly journals Structures of Complexes Formed by HIV-1 Reverse Transcriptase at a Termination Site of DNA Synthesis

2001 ◽  
Vol 276 (33) ◽  
pp. 31439-31448 ◽  
Author(s):  
Marc Lavigne ◽  
Lucette Polomack ◽  
Henri Buc
Keyword(s):  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Hiv 1

scholarly journals Mutating a Region of HIV-1 Reverse Transcriptase Implicated in tRNALys-3Binding and the Consequences for (−)-Strand DNA Synthesis

1998 ◽  
Vol 273 (23) ◽  
pp. 14523-14532 ◽  
Author(s):  
Eric J. Arts ◽  
Jennifer T. Miller ◽  
Bernard Ehresmann ◽  
Stuart F. J. Le Grice
Keyword(s):  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Hiv 1

The double mutation L109M and R448M of HIV-1 reverse transcriptase decreases fidelity of DNA synthesis by promoting mismatch elongation

2015 ◽  
Vol 396 (12) ◽  
pp. 1315-1323
Author(s):  
Bianca Heyn ◽  
Nicole Pogodalla ◽  
Susanne Brakmann
Keyword(s):  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Error Rate ◽  
Double Mutant ◽  
Dissociation Rate ◽  
Double Mutation ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Simultaneous Substitution

Abstract Changes of Leu109 and Arg448 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have as yet not been associated with altered fitness. However, in a recent study, we described that the simultaneous substitution of L109 and R448 by methionine leads to an error-producing polymerase phenotype that is not observed for the isolated substitutions. The double mutant increased the error rate of DNA-dependent DNA synthesis 3.1-fold as compared to the wildtype enzyme and showed a mutational spectrum with a fraction of 28% frameshift mutations and 48% transitions. We show here that weaker binding of DNA:DNA primer-templates as indicated by an increased dissociation rate constant (koff) could account for the higher frameshift error rate. Furthermore, we were able to explain the prevalence of transition mutations with the finding that HIV-1 RT variant L109M/R448M preferred misincorporation of C opposite A and elongation of C:A mismatches.

scholarly journals Effect of template secondary structure on the inhibition of HIV-1 reverse transcriptase by a pyridinone non-nucleoside inhibitor

1994 ◽  
Vol 22 (8) ◽  
pp. 1437-1443 ◽  
Author(s):  
David B. Oisen ◽  
Steven S. Carroll ◽  
J.Chris Culberson ◽  
Jules A. Shafer ◽  
Lawrence C. Kuo
Keyword(s):  
Secondary Structure ◽  
Reverse Transcriptase ◽  
Hiv 1

scholarly journals In-Depth Analysis of the Interaction of HIV-1 with Cellular microRNA Biogenesis and Effector Mechanisms

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Adam W. Whisnant ◽  
Hal P. Bogerd ◽  
Omar Flores ◽  
Phong Ho ◽  
Jason G. Powers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Secondary Structure ◽  
Mirna Expression ◽  
Binding Sites ◽  
Rna Secondary Structure ◽  
Cellular Mirnas ◽  
Viral Mirnas ◽  
Depth Analysis ◽  
Hiv 1 ◽  
Effector Mechanisms

ABSTRACTThe question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4+peripheral blood mononuclear cells [PBMCs] and macrophages) to unequivocally demonstrate that HIV-1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV-1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV-1 genome using the photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV-1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV-1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV-1 transcripts have evolved to avoid inhibition by preexisting cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites.IMPORTANCEMicroRNAs (miRNAs) are a ubiquitous class of small regulatory RNAs that serve as posttranscriptional regulators of gene expression. Previous work has suggested that HIV-1 might subvert the function of the cellular miRNA machinery by expressing viral miRNAs or by dramatically altering the level of cellular miRNA expression. Using very sensitive approaches, we now demonstrate that neither of these ideas is in fact correct. Moreover, HIV-1 transcripts appear to largely avoid regulation by cellular miRNAs by adopting an extensive RNA secondary structure that occludes the ability of cellular miRNAs to interact with viral mRNAs. Together, these data suggest that HIV-1, rather than seeking to control miRNA function in infected cells, has instead evolved a mechanism to become largely invisible to cellular miRNA effector mechanisms.

Sign in / Sign up

Export Citation Format

Share Document