Evidence map›Paper›PMID 25768906›Full record

ArticleCell2015

Hepatitis C virus RNA functionally sequesters miR-122.

Joseph M Luna, Troels K H Scheel, Tal Danino, Katharina S Shaw, Aldo Mele, John J Fak, Eiko Nishiuchi, Constantin N Takacs, Maria Teresa Catanese, Ype P de Jong and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers.

0numbers the graph read from it
0cells of the map it votes in
218citing papers in PubMed
25.5field-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

218 citing papers in PubMed, 334 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

158 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Joseph M LunaLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Troels K H ScheelLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Disease and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, and Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Tal DaninoLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Katharina S ShawLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
Aldo MeleLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
John J FakLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Eiko NishiuchiLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
Constantin N TakacsLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065, USA.
Maria Teresa CataneseLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
Ype P de JongLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Center for the Study of Hepatitis C, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
Ira M JacobsonCenter for the Study of Hepatitis C, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
Charles M RiceLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA. Electronic address: ricec@rockefeller.edu.
Robert B DarnellLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA. Electronic address: darnelr@rockefeller.edu.
Rockefeller University · USHoward Hughes Medical Institute · USCopenhagen University Hospital · DKCornell University · US

Funding

TRANSFORMING TRANSLATIONAL SCIENCE AND EDUCATION TO BENEFIT HUMAN HEALTHUL1RR024143 · NCRR · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2006 to 2011
$49.1M
NEUROLOGY AND THE MOLECULAR ROLE OF N-RBPS IN THE BRAINR01NS034389 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 1995 to 2016
$6.3M
Modeling human hepatotropic infections in complex tissue organoidsR01DK085713 · NIDDK · ROCKEFELLER UNIVERSITY · PI BHATIA, SANGEETA N., RICE, CHARLES M · 2009 to 2013
$5.6M
Type I interferon-stimulated genes and the antiviral immune responseR01AI091707 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2011 to 2020
$5.5M
Mapping the mechanisms of protein synthesis-dependent synaptic plasticityR01NS081706 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 2012 to 2016
$5.3M
Structure and function of the HCV RNA replicaseR01CA057973 · NCI · WASHINGTON UNIVERSITY · PI RICE, CHARLES M · 1992 to 2013
$4.7M
Identification and characterization of cellular factors involved in HCV entryR01AI072613 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2007 to 2016
$4.7M
Hepatitis C antivirals: Mechanism of action, combination efficacy and resistanceR01AI099284 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2012 to 2016
$3.6M
Role of HCV p7 and NS2 in infectious virus productionR01AI075099 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2008 to 2012
$2.1M
Simianizing hepatitis C: Defining the species-tropism of a hepatotropic virusR01AI090055 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2010 to 2014
$2.1M
The role of innate immune evasion in hepatitis C virus infectionK08DK090576 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI DE JONG, YPE PETER · 2011 to 2015
$760k
Neurology and the molecular role of N-RBPs in the brainR56NS034389 · NINDS · ROCKEFELLER UNIVERSITY · PI DARNELL, ROBERT B · 2012 to 2012
$590k
Howard Hughes Medical InstituteNCI NIH HHS CA057973NCI NIH HHS R01 CA057973NCRR NIH HHS UL1 RR024143NCRR NIH HHS UL1RR024143NIAID NIH HHS AI072613NIAID NIH HHS AI075099NIAID NIH HHS AI090055NIAID NIH HHS AI091707NIAID NIH HHS AI099284NIAID NIH HHS R01 AI072613NIAID NIH HHS R01 AI075099NIAID NIH HHS R01 AI090055NIAID NIH HHS R01 AI091707NIAID NIH HHS R01 AI099284NIDDK NIH HHS DK085713NIDDK NIH HHS K08 DK090576NIDDK NIH HHS R01 DK085713NINDS NIH HHS NS034389NINDS NIH HHS NS081706NINDS NIH HHS R01 NS034389NINDS NIH HHS R01 NS081706
6 · The paper itself

Abstract

Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On the human transcriptome, we observed reduced AGO binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 "sponge" effect was relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV-induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV.

Indexed as

Argonaute ProteinsBase SequenceCell Line, TumorEukaryotic Initiation FactorsHepacivirusHepatitis CHumansLiverMicroRNAsMolecular Sequence DataRNA, ViralVirus ReplicationAGO1 protein, humanArgonaute ProteinsEukaryotic Initiation FactorsMicroRNAsMIRN122 microRNA, humanRNA, Viral

Identifiers

PMID25768906
PMCPMC4386883
OpenAlexW1986944906

What OpenQuestion holds

Textmetadata
LicenceTDM
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.