ArticleJournal of virology1999
A hairpin structure in the R region of the human immunodeficiency virus type 1 RNA genome is instrumental in polyadenylation site selection.
Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed.
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Involvement of Human Cellular Proteins and Structures in Realization of the HIV Life Cycle: A Comprehensive Review, 2024.Viruses · 2024Review
- Role of RNA structural plasticity in modulating HIV-1 genome packaging and translation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Origin and functional role of antisense transcription in endogenous and exogenous retroviruses.Retrovirology · 2023Review
- Article
- Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms.Scientific reports · 2020Article
- Identification of the initial nucleocapsid recognition element in the HIV-1 RNA packaging signal.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Anomalous Reverse Transcription through Chemical Modifications in Polyadenosine Stretches.Biochemistry · 2020Article
- Combination Immune Checkpoint Blockade to Reverse HIV Latency.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Diverse effects of interferon alpha on the establishment and reversal of HIV latency.PLoS pathogens · 2020Article
- On the generation of the MSD-Ѱ class of defective HIV proviruses.Retrovirology · 2019Article
- HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry.The Journal of biological chemistry · 2019Article
- In cell mutational interference mapping experiment (in cell MIME) identifies the 5' polyadenylation signal as a dual regulator of HIV-1 genomic RNA production and packaging.Nucleic acids research · 2018Article
- HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike.Journal of virology · 2016Article
- A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal.Viruses · 2016Article
- Minor Contribution of Chimeric Host-HIV Readthrough Transcripts to the Level of HIV Cell-Associated gag RNA.Journal of virology · 2016Article
- Strong epistatic selection on the RNA secondary structure of HIV.PLoS pathogens · 2014Article
- Small-angle X-ray scattering-derived structure of the HIV-1 5' UTR reveals 3D tRNA mimicry.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- In vivo SELEX of single-stranded domains in the HIV-1 leader RNA.Journal of virology · 2014Article
17 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
Some retroviruses with an extended repeat (R) region encode the polyadenylation signal within the R region such that this signal is present at both the 5' and 3' ends of the viral transcript. This necessitates differential regulation to either repress recognition of the 5' polyadenylation signal or enhance usage of the 3' signal. The human immunodeficiency virus type 1 (HIV-1) genome encodes an inherently efficient polyadenylation signal within the 97-nucleotide R region. Polyadenylation at the 5' HIV-1 polyadenylation site is inhibited by downstream splicing signals, and usage of the 3' polyadenylation site is triggered by an upstream enhancer element. In this paper, we demonstrate that this on-off switch of the HIV-1 polyadenylation signal is controlled by a secondary RNA structure that occludes part of the AAUAAA hexamer motif, which we have termed the polyA hairpin. Opening the 5' hairpin by mutation triggered premature polyadenylation and caused reduced synthesis of viral RNA, indicating that the RNA structure plays a pivotal role in repression of the 5' polyadenylation site. Apparently, the same hairpin structure does not interfere with efficient usage of the 3' polyadenylation site, which may be due to the presence of the upstream enhancer element. However, when the 3' hairpin was further stabilized by mutation, we measured a complete loss of 3' polyadenylation. Thus, the thermodynamic stability of the polyA hairpin is delicately balanced to allow nearly complete repression of the 5' site yet efficient activation of the 3' site. This is the first report of regulated polyadenylation that is mediated by RNA secondary structure. A similar hairpin motif that occludes the polyadenylation signal can be proposed for other lentiviruses and members of the spumaretroviruses, suggesting that this represents a more general gene expression strategy of complex retroviruses.
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