ArticleNucleic acids research2018
Identification of conserved, primary sequence motifs that direct retrovirus RNA fate.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Putting a Kink in HIV-1 Particle Infectivity: Rocaglamide Inhibits HIV-1 Replication by Altering Gag-Genomic RNA Interaction.Viruses · 2024Article
- Retroviral PBS-segment sequence and structure: Orchestrating early and late replication events.Retrovirology · 2024Review
- The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression.Nature communications · 2024Article
- Anomalous HIV-1 RNA, How Cap-Methylation Segregates Viral Transcripts by Form and Function.Viruses · 2022Review
- HIV-1 hypermethylated guanosine cap licenses specialized translation unaffected by mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The CD8Microbiology and molecular biology reviews : MMBR · 2021Review
- Overview of the Nucleic-Acid Binding Properties of the HIV-1 Nucleocapsid Protein in Its Different Maturation States.Viruses · 2020Review
- Article
- 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
- The mRNA encoding the JUND tumor suppressor detains nuclear RNA-binding proteins to assemble polysomes that are unaffected by mTOR.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Precise stoichiometry of genome-length transcripts and alternatively spliced mRNAs is a hallmark of retroviruses. We discovered short, guanosine and adenosine sequence motifs in the 5'untranslated region of several retroviruses and ascertained the reasons for their conservation using a representative lentivirus and genetically simpler retrovirus. We conducted site-directed mutagenesis of the GA-motifs in HIV molecular clones and observed steep replication delays in T-cells. Quantitative RNA analyses demonstrate the GA-motifs are necessary to retain unspliced viral transcripts from alternative splicing. Mutagenesis of the GA-motifs in a C-type retrovirus validate the similar downregulation of unspliced transcripts and virion structural protein. The evidence from cell-based co-precipitation studies shows the GA-motifs in the 5'untranslated region confer binding by SFPQ/PSF, a protein co-regulated with T-cell activation. Diminished SFPQ/PSF or mutation of either GA-motif attenuates the replication of HIV. The interaction of SFPQ/PSF with both GA-motifs is crucial for maintaining the stoichiometry of the viral transcripts and does not affect packaging of HIV RNA. Our results demonstrate the conserved GA-motifs direct the fate of retrovirus RNA. These findings have exposed an RNA-based molecular target to attenuate retrovirus replication.
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Registered trials
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