Evidence map›Paper›PMID 21220300›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Masking the 5' terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex.

Erica S Machlin, Peter Sarnow, Selena M Sagan

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed, 1 pooled it
13.5field-weighted citation impact, top 1% 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

156 citing papers in PubMed, 1 synthesis or guideline pooled it, 276 citations in OpenAlex.

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  15. Subversion of a protein-microRNA signaling pathway by hepatitis C virus.Proceedings of the National Academy of Sciences of the United States of America · 2023
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96 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Erica S MachlinDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Peter Sarnow
Selena M Sagan
Stanford University · USDuke University · US

Funding

MOLECULAR BASIS OF HOST-PARASITE INTERACTIONT32AI007328 · NIAID · STANFORD UNIVERSITY · PI JUSTIN L SONNENBURG · 1987 to 2026
$11.9M
Roles for microRNA-122 in hepatitis C virus RNA amplificationR01AI069000 · NIAID · STANFORD UNIVERSITY · PI SARNOW, PETER · 2006 to 2022
$6.2M
Structure and Function of the Hepatitis C Virus GenomeR37AI047365 · NIAID · STANFORD UNIVERSITY · PI SARNOW, PETER · 2011 to 2019
$4.0M
THE PROKARYOTIC-LIKE IRES IN HCV AS A DRUG TARGETR01AI047365 · NIAID · STANFORD UNIVERSITY · PI PUGLISI, JOSEPH D, SARNOW, PETER · 1999 to 2010
$3.8M
Roles for virus-derived circular RNAs during RNA virus infectionsR56AI069000 · NIAID · STANFORD UNIVERSITY · PI SARNOW, PETER · 2025 to 2025
$634k
NIAID NIH HHS AI069000NIAID NIH HHS AI47365NIAID NIH HHS R01 AI047365NIAID NIH HHS R01 AI069000NIAID NIH HHS R37 AI047365NIAID NIH HHS R56 AI069000NIAID NIH HHS T32 AI007328
6 · The paper itself

Abstract

Hepatitis C virus subverts liver-specific microRNA, miR-122, to upregulate viral RNA abundance in both infected cultured cells and in the liver of infected chimpanzees. These findings have identified miR-122 as an attractive antiviral target. Thus, it is imperative to know whether a distinct functional complex exists between miR-122 and the viral RNA versus its normal cellular target mRNAs. Toward this goal, effects on viral RNA abundance of mutated miR-122 duplex molecules, bound at each of the two target sites in the viral genome, were compared to effects on microRNA- or siRNA-mediated regulation of reporter target mRNAs. It was found that miR-122 formed an unusual microRNA complex with the viral RNA that is distinct from miR-122 complexes with reporter mRNAs. Notably, miR-122 forms an oligomeric complex in which one miR-122 molecule binds to the 5' terminus of the hepatitis C virus (HCV) RNA with 3' overhanging nucleotides, masking the 5' terminal sequences of the HCV genome. Furthermore, specific internal nucleotides as well as the 3' terminal nucleotides in miR-122 were absolutely required for maintaining HCV RNA abundance but not for microRNA function. Both miR-122 molecules utilize similar internal nucleotides to interact with the viral genome, creating a bulge and tail in the miR-122 molecules, revealing tandemly oriented oligomeric RNA complexes. These findings suggest that miR-122 protects the 5' terminal viral sequences from nucleolytic degradation or from inducing innate immune responses to the RNA terminus. Finally, this remarkable microRNA-mRNA complex could be targeted with compounds that inactivate miR-122 or interfere with this unique RNA structure.

Indexed as

5' Flanking RegionAnimalsBase SequenceBinding SitesGene Expression RegulationGenome, ViralHepacivirusHost-Pathogen InteractionsMicroRNAsNucleic Acid ConformationPan troglodytesRNA, ViralMicroRNAsRNA, Viral

Identifiers

PMID21220300
PMCPMC3044371
OpenAlexW2089462743

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.