ArticleJournal of virology2002
The tRNA primer activation signal in the human immunodeficiency virus type 1 genome is important for initiation and processive elongation of reverse transcription.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Human T-cell leukemia virus type 1 uses a specific tRNARNA (New York, N.Y.) · 2024Article
- Retroviral PBS-segment sequence and structure: Orchestrating early and late replication events.Retrovirology · 2024Review
- HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes.Nature communications · 2024Article
- Reverse transcription of plasma-derived HIV-1 RNA generates multiple artifacts through tRNA(Lys-3)-priming.Microbiology spectrum · 2024Article
- Review
- Review
- The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.Nucleic acids research · 2021Article
- High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs.Nature communications · 2021Article
- Extended Interactions between HIV-1 Viral RNA and tRNAInternational journal of molecular sciences · 2020Article
- Article
- Distinct Conformational States Underlie Pausing during Initiation of HIV-1 Reverse Transcription.Journal of molecular biology · 2020Article
- Relating Structure and Dynamics in RNA Biology.Cold Spring Harbor perspectives in biology · 2019Review
- Intrinsic conformational dynamics of the HIV-1 genomic RNA 5'UTR.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication.The Journal of biological chemistry · 2019Review
- Dynamic Interplay of RNA and Protein in the Human Immunodeficiency Virus-1 Reverse Transcription Initiation Complex.Journal of molecular biology · 2018Article
- Article
- A Fourth Generation Lentiviral Vector: Simplifying Genomic Gymnastics.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Reverse Transcription in the Saccharomyces cerevisiae Long-Terminal Repeat Retrotransposon Ty3.Viruses · 2017Review
- Heterogeneous structures formed by conserved RNA sequences within the HIV reverse transcription initiation site.RNA (New York, N.Y.) · 2016Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) reverse transcription is primed by the cellular tRNA(3)(Lys) molecule, which binds, with its 3"-terminal 18 nucleotides (nt), to a complementary sequence in the viral genome, the primer-binding site (PBS). Besides PBS-anti-PBS pairing, additional interactions between viral RNA sequences and the tRNA primer are thought to regulate the process of reverse transcription. We previously identified a novel 8-nt sequence motif in the U5 region of the HIV-1 RNA genome that is critical for tRNA(3)(Lys)-mediated initiation of reverse transcription in vitro. This motif activates initiation from the natural tRNA(3)(Lys) primer but is not involved in tRNA placement and was therefore termed primer activation signal (PAS). It was proposed that the PAS interacts with the anti-PAS motif in the TphiC arm of tRNA(3)(Lys). In this study, we analyzed several PAS-mutated viruses and performed reverse transcription assays with virion-extracted RNA-tRNA complexes. Mutation of the PAS reduced the efficiency of tRNA-primed reverse transcription. In contrast, mutations in the opposing leader sequence that trigger release of the PAS from base pairing stimulated reverse transcription. These results are similar to the reverse transcription effects observed in vitro. We also selected revertant viruses that partially overcome the reverse transcription defect of the PAS deletion mutant. Remarkably, all revertants acquired a single nucleotide substitution that does not restore the PAS sequence but that stimulates elongation of reverse transcription. These combined results indicate that the additional PAS-anti-PAS interaction is needed to assemble an initiation-competent and processive reverse transcription complex.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.