Hepatitis C virus RNA functionally sequesters miR-122

Cell
Joseph M LunaRobert B Darnell

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.

References

Jun 5, 2002·Genome Research·W James KentDavid Haussler
Nov 20, 2002·Journal of Virology·Keril J BlightCharles M Rice
Jun 11, 2005·Science·Brett D LindenbachCharles M Rice
Sep 6, 2005·Science·Catherine L JoplingPeter Sarnow
Feb 7, 2006·Cell Metabolism·Christine EsauBrett P Monia
Aug 26, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Anna-Karin Sohlenius-Sternbeck
Jul 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Glenn RandallCharles M Rice
Nov 13, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Svetlana MarukianLynn B Dustin
Nov 21, 2008·The EMBO Journal·Jura Inga HenkeMichael Niepmann
Jan 17, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Judith M GottweinJens Bukh
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Jun 3, 2009·Genes & Development·David GatfieldUeli Schibler
Jul 28, 2009·Gastroenterology·Yuqiong LiangStanley M Lemon
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Feb 2, 2010·Nature Biotechnology·Christopher T JonesCharles M Rice
Jun 19, 2010·Science·Demián CazallaJoan A Steitz
Dec 28, 2010·Virology·Neda NasheriJohn Paul Pezacki
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Erica S MachlinSelena M Sagan
Mar 3, 2011·The Journal of Clinical Investigation·Mirco CastoldiMartina U Muckenthaler
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yi-Ping LiJens Bukh
Jun 3, 2011·Nature Biotechnology·Chaolin Zhang, Robert B Darnell
Aug 2, 2011·Cell·Leonardo SalmenaPier Paolo Pandolfi
Aug 23, 2011·Nature Genetics·Shankar MukherjiAlexander van Oudenaarden
Nov 11, 2011·Journal of Virology·Phillip S PangJeffrey S Glenn
Jan 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tetsuro ShimakamiStanley M Lemon
Jan 14, 2012·Nucleic Acids Research·Fanglei ZhuangG Brett Robb
Feb 1, 2012·PLoS Pathogens·Rebecca L SkalskyBryan R Cullen
Jul 24, 2012·The Journal of Clinical Investigation·Shu-Hao HsuKalpana Ghoshal
Jul 24, 2012·The Journal of Clinical Investigation·Wei-Chih TsaiAnn-Ping Tsou
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·You LiStanley M Lemon
Mar 29, 2013·The New England Journal of Medicine·Harry L A JanssenMichael R Hodges

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Citations

Oct 11, 2015·Virus Research·Elena Carnero, Puri Fortes
Feb 3, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jennifer Y Tan, Ana C Marques
Jun 23, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Amir Shlomai
Mar 8, 2016·Wiley Interdisciplinary Reviews. Developmental Biology·Bruno R SteinkrausTudor A Fulga
Mar 11, 2016·Cell Host & Microbe·Troels K H ScheelCharles M Rice
Oct 24, 2015·Trends in Endocrinology and Metabolism : TEM·Sean M HartigSean E McGuire
Oct 7, 2015·Chemistry : a European Journal·Takeo FukuzumiKazuhiko Nakatani
Oct 20, 2015·Nature Chemical Biology·Ragunath SingaraveluJohn Paul Pezacki
Jul 15, 2015·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·V SchinzariS Piconese
Jun 5, 2016·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Zoya B Kurago
Feb 29, 2016·Trends in Genetics : TIG·Yunfei WangYiwen Chen
Apr 8, 2015·RNA Biology·Jana McCaskillAmy H Buck
Apr 5, 2016·Nature Reviews. Genetics·Daniel W Thomson, Marcel E Dinger
Jun 3, 2015·Journal of Cellular Physiology·Jin WangSubrata Sen
Apr 10, 2016·Reviews in Medical Virology·Diogo Piedade, José Miguel Azevedo-Pereira
Aug 11, 2015·Nature Reviews. Microbiology·You LiStanley M Lemon
Jul 29, 2015·Infectious Agents and Cancer·Zhao WangAjit Kumar
Jul 15, 2015·Médecine sciences : M/S·Chloé Mengardi, Théophile Ohlmann
Apr 11, 2015·Frontiers in Oncology·Kaveri SidhuVijay Kumar
Apr 19, 2015·Journal of Hematology & Oncology·Avencia Sanchez-Mejias, Yvonne Tay
Oct 27, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Changming LiuDaping Xiao
May 7, 2016·Viruses·Angela CiuffiAmalio Telenti
May 27, 2016·Journal of Human Genetics·Motoyuki OtsukaKazuhiko Koike
Jun 9, 2016·Viruses·Diogo Piedade, José Miguel Azevedo-Pereira
Jun 14, 2016·Neoplasia : an International Journal for Oncology Research·Mark P HamiltonSean E McGuire
Jul 13, 2016·Scientific Reports·Vanmathy Kasimanickam, John Kastelic
Jul 13, 2016·Reviews in Medical Virology·Nikhil Sharma, Sunit K Singh
Aug 1, 2016·Current Opinion in Virology·Megan H PowdrillJohn Paul Pezacki
Aug 10, 2016·Current Opinion in Virology·Elham Shirvani-DastgerdiAlexander Ploss
Apr 26, 2016·British Journal of Clinical Pharmacology·Kannan Sridharan, Nithya Jaideep Gogtay
Sep 20, 2016·Journal of Hepatology·Darius MoradpourMichael P Manns
Oct 6, 2016·Journal of Hepatology·Christoph Roderburg, Christian Trautwein
Sep 1, 2016·Annual Review of Virology·Peter Sarnow, Selena M Sagan
Jan 1, 2015·Uirusu·Takahiro Masaki, Stanley Lemon
Nov 3, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·N GoldaracenaM Selzner

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