ArticleProceedings of the National Academy of Sciences of the United States of America2021
Selective packaging of HIV-1 RNA genome is guided by the stability of 5' untranslated region polyA stem.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Transcription start site heterogeneity controls MDA5 sensing of unspliced HIV-1 RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- GABARAP proteins regulate the packaging of HIV-1 genomic RNA into virions.EMBO reports · 2025Article
- DEAD-box helicase intrinsically disordered domains and structural dynamics of HIV-1 RNA are required to reveal DDX3X catalytic efficiency.Nucleic acids research · 2025Article
- 5' cap sequestration is required for sensing of unspliced HIV-1 RNA by MDA5.bioRxiv : the preprint server for biology · 2025Article
- How to recover from a bad start: adaptation of HIV-1 transcription start site mutants during serial passaging in culture.Journal of virology · 2025Article
- Elements in the 5' Untranslated Region of Viral RNA Important for HIV Gag Recognition and Cross-Packaging.Viruses · 2025Article
- Structures of complete HIV-1 TAR RNA portray a dynamic platform poised for protein binding and structural remodeling.Nature communications · 2025Article
- Article
- Translation of HIV-1 unspliced RNA is regulated by 5' untranslated region structure.Journal of virology · 2024Article
- Transcription start site choice regulates HIV-1 RNA conformation and function.Current opinion in structural biology · 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
- Retroviral PBS-segment sequence and structure: Orchestrating early and late replication events.Retrovirology · 2024Review
- HIV-1 RNA genome packaging: it's G-rated.mBio · 2024Review
- HIV-1 RNAs whose transcription initiates from the third deoxyguanosine of GGG tract in the 5' long terminal repeat serve as a dominant genome for efficient provirus DNA formation.Journal of virology · 2024Article
- HIV-1 Gag co-localizes with euchromatin histone marks at the nuclear periphery.Journal of virology · 2023Article
- Structure of the HIV immature lattice allows for essential lattice remodeling within budded virions.eLife · 2023Article
- HIV-1 usurps transcription start site heterogeneity of host RNA polymerase II to maximize replication fitness.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Nano-DMS-MaP allows isoform-specific RNA structure determination.Nature methods · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
To generate infectious virus, HIV-1 must package two copies of its full-length RNA into particles. HIV-1 transcription initiates from multiple, neighboring sites, generating RNA species that only differ by a few nucleotides at the 5' end, including those with one (1G) or three (3G) 5' guanosines. Strikingly, 1G RNA is preferentially packaged into virions over 3G RNA. We investigated how HIV-1 distinguishes between these nearly identical RNAs using in-gel chemical probing combined with recently developed computational tools for determining RNA conformational ensembles, as well as cell-based assays to quantify the efficiency of RNA packaging into viral particles. We found that 1G and 3G RNAs fold into distinct structural ensembles. The 1G RNA, but not the 3G RNA, primarily adopts conformations with an intact polyA stem, exposed dimerization initiation site, and multiple, unpaired guanosines known to mediate Gag binding. Furthermore, we identified mutants that exhibited altered genome selectivity and packaged 3G RNA efficiently. In these mutants, both 1G and 3G RNAs fold into similar conformational ensembles, such that they can no longer be distinguished. Our findings demonstrate that polyA stem stability guides RNA-packaging selectivity. These studies also uncover the mechanism by which HIV-1 selects its genome for packaging: 1G RNA is preferentially packaged because it exposes structural elements that promote RNA dimerization and Gag binding.
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