Abstract
BackgroundTwo hairpin structures that are present at both the 5' and 3' end of the HIV-1 RNA genome have important functions in the viral life cycle. The TAR hairpin binds the viral Tat protein and is essential for Tat-mediated activation of transcription. The adjacent polyA hairpin encompasses the polyadenylation signal AAUAAA and is important for the regulation of polyadenylation. Specifically, this RNA structure represses polyadenylation at the 5' side, and enhancer elements on the 3' side overcome this suppression. We recently described that the replication of an HIV-1 variant that does not need TAR for transcription was severely impaired by destabilization of the TAR hairpin, even though a complete TAR deletion was acceptable.ResultsIn this study, we show that the TAR-destabilizing mutations result in reduced 3' polyadenylation of the viral transcripts due to an extension of the adjacent polyA hairpin. Thus, although the TAR hairpin is not directly involved in polyadenylation, mutations in TAR can affect this process.ConclusionThe stability of the HIV-1 TAR hairpin structure is important for the proper folding of the viral RNA transcripts. This study illustrates how mutations that are designed to study the function of a specific RNA structure can change the structural presentation of other RNA domains and thus affect viral replication in an indirect way.
Highlights
Two hairpin structures that are present at both the 5' and 3' end of the HIV-1 RNA genome have important functions in the viral life cycle
We propose that unpaired TAR nucleotides extend the polyA hairpin, restricting the availability of the AAUAAA signal for cleavage polyadenylation specificity factor (CPSF) binding and polyadenylation
HIV-rtTA expression is reduced by destabilization but not by truncation of the TAR hairpin We previously demonstrated that the TAR-destabilizing A and B mutations induce an alternative folding at the 5' end of the HIV-rtTA transcripts
Summary
Two hairpin structures that are present at both the 5' and 3' end of the HIV-1 RNA genome have important functions in the viral life cycle. The adjacent polyA hairpin encompasses the polyadenylation signal AAUAAA and is important for the regulation of polyadenylation This RNA structure represses polyadenylation at the 5' side, and enhancer elements on the 3' side overcome this suppression. The 97-nt R region in HIV-1 RNA can fold two stem-loop structures, the TAR and polyA hairpins (Fig. 1A). Both motifs have important functions in the biosynthesis of viral transcripts. It was demonstrated that pTEFb directs the recruitment of TATA-box-binding protein (TBP) to the LTR promoter to stimulate the assembly of (page number not for citation purposes)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
