Evidence map›Paper›PMID 24938790›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production.

Antony K Chen, Prabuddha Sengupta, Kayoko Waki, Schuyler B Van Engelenburg, Takahiro Ochiya, Sherimay D Ablan, Eric O Freed, Jennifer Lippincott-Schwartz

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. Challenging Cellular Homeostasis: Spatial and Temporal Regulation of miRNAs.International journal of molecular sciences · 2022
    Review
  10. Article
  11. Article
  12. Review
  13. The involvement of microRNAs in HCV and HIV infection.Therapeutic advances in vaccines and immunotherapy · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Antony K ChenEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China;
Prabuddha SenguptaEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
Kayoko WakiVirus-Cell Interaction Section, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; and.
Schuyler B Van EngelenburgEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
Takahiro OchiyaDivision of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Sherimay D AblanVirus-Cell Interaction Section, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; and.
Eric O FreedVirus-Cell Interaction Section, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; and.
Jennifer Lippincott-SchwartzEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; lippincj@mail.nih.gov.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Cancer Institute · USFrederick National Laboratory for Cancer Research · US

Funding

Organization and Dynamics of Endomembrane Pathways and OrganellesZIAHD001609 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BONIFACINO, JUAN · 2009 to 2019
$16.2M
Retroviral Gag Trafficking, Env Incorporation, and Virus AssemblyZIABC010775 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI FREED, ERIC · 2009 to 2015
$4.6M
6 · The paper itself

Abstract

MicroRNAs (miRNAs) are small, 18-22 nt long, noncoding RNAs that act as potent negative gene regulators in a variety of physiological and pathological processes. To repress gene expression, miRNAs are packaged into RNA-induced silencing complexes (RISCs) that target mRNAs for degradation and/or translational repression in a sequence-specific manner. Recently, miRNAs have been shown to also interact with proteins outside RISCs, impacting cellular processes through mechanisms not involving gene silencing. Here, we define a previously unappreciated activity of miRNAs in inhibiting RNA-protein interactions that in the context of HIV-1 biology blocks HIV virus budding and reduces virus infectivity. This occurs by miRNA binding to the nucleocapsid domain of the Gag protein, the main structural component of HIV-1 virions. The resulting miRNA-Gag complexes interfere with viral-RNA-mediated Gag assembly and viral budding at the plasma membrane, with imperfectly assembled Gag complexes endocytosed and delivered to lysosomes. The blockade of virus production by miRNA is reversed by adding the miRNA's target mRNA and stimulated by depleting Argonaute-2, suggesting that when miRNAs are not mediating gene silencing, they can block HIV-1 production through disruption of Gag assembly on membranes. Overall, our findings have significant implications for understanding how cells modulate HIV-1 infection by miRNA expression and raise the possibility that miRNAs can function to disrupt RNA-mediated protein assembly processes in other cellular contexts.

Indexed as

Argonaute ProteinsCluster AnalysisDNA PrimersHEK293 CellsHIV-1HumansMicroRNAsMicroscopy, FluorescenceMultiprotein ComplexesProtein PrecursorsRNA, Small InterferingVirus AssemblyVirus ReleaseAGO2 protein, humanArgonaute ProteinsDNA PrimersMicroRNAsMultiprotein Complexesp55 gag precursor protein, Human immunodeficiency virus 1Protein PrecursorsRNA, Small Interfering

Identifiers

PMID24938790
PMCPMC4084429
OpenAlexW2151314962

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.