DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Geon-Woo | ko |
dc.contributor.author | Lee, Seung-Hoon | ko |
dc.contributor.author | Cho, Hee | ko |
dc.contributor.author | Kim, Minwoo | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Oh, Jong-Won | ko |
dc.date.accessioned | 2016-11-09T05:36:13Z | - |
dc.date.available | 2022-06-02T21:00:55Z | - |
dc.date.created | 2016-10-19 | - |
dc.date.created | 2016-10-19 | - |
dc.date.issued | 2016-07 | - |
dc.identifier.citation | PLOS PATHOGENS, v.12, no.7 | - |
dc.identifier.issn | 1553-7366 | - |
dc.identifier.uri | http://hdl.handle.net/10203/213811 | - |
dc.description.abstract | The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3' end by 3'-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3'-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3' end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation | - |
dc.language | English | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.subject | VIRAL-RNA POLYMERASE | - |
dc.subject | CYTOPLASMIC POLY(A) POLYMERASE | - |
dc.subject | TUMOR-SUPPRESSOR MICRORNA | - |
dc.subject | IN-VIVO | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | HEPATOCELLULAR-CARCINOMA | - |
dc.subject | LIFE-CYCLE | - |
dc.subject | LIVER | - |
dc.subject | REPLICATION | - |
dc.subject | INFECTION | - |
dc.title | Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2 | - |
dc.type | Article | - |
dc.identifier.wosid | 000383366400014 | - |
dc.identifier.scopusid | 2-s2.0-84982946405 | - |
dc.type.rims | ART | - |
dc.citation.volume | 12 | - |
dc.citation.issue | 7 | - |
dc.citation.publicationname | PLOS PATHOGENS | - |
dc.identifier.doi | 10.1371/journal.ppat.1005714 | - |
dc.embargo.terms | 2017-04-02 | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Kim, Geon-Woo | - |
dc.contributor.nonIdAuthor | Lee, Seung-Hoon | - |
dc.contributor.nonIdAuthor | Cho, Hee | - |
dc.contributor.nonIdAuthor | Kim, Minwoo | - |
dc.contributor.nonIdAuthor | Oh, Jong-Won | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | VIRAL-RNA POLYMERASE | - |
dc.subject.keywordPlus | CYTOPLASMIC POLY(A) POLYMERASE | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR MICRORNA | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | LIFE-CYCLE | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | REPLICATION | - |
dc.subject.keywordPlus | INFECTION | - |
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