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In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization. An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA. We found that NS5A bound to GU-rich elements in vitro and in cells. Mutation of the NS5A zinc finger abrogated its GU-rich element-binding and mRNA stabilizing activities. Overall, we identified a molecular mechanism whereby HCV manipulates host gene expression by stabilizing host transcripts in a manner that would promote growth and prevent death of virus-infected cells, allowing the virus to establish chronic infection and lead to the development of hepatocellular carcinoma.<\/jats:p>","DOI":"10.1093\/nar\/gky061","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T20:11:16Z","timestamp":1516651876000},"page":"2537-2547","source":"Crossref","is-referenced-by-count":7,"title":["The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts"],"prefix":"10.1093","volume":"46","author":[{"given":"Liang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology Training Program, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Graduate Program in Comparative and Molecular Bioscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh D","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, The Pennsylvania State University 201 Althouse Laboratory, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose D","family":"Debes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Beisang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Rattenbacher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina Vlasova-St","family":"Louis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darin L","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig E","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, The Pennsylvania State University 201 Althouse Laboratory, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R","family":"Bohjanen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology Training Program, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Graduate Program in Comparative and Molecular Bioscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,1,29]]},"reference":[{"key":"2019122103585310900_B1","doi-asserted-by":"crossref","first-page":"7396","DOI":"10.1128\/JVI.79.12.7396-7401.2005","article-title":"The exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable","volume":"79","author":"Glaunsinger","year":"2005","journal-title":"J. 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