microRNA-122 stimulates translation of hepatitis C virus RNA

By J. Henke, D. Goergen, Junfeng Zheng, Yutong Song, C. Schüttler, Carmen Fehr, Christiane Jünemann, M. Niepmann. EMBO Journal, 2008

729 citations recorded by the source corpus.

Hepatitis C virus (HCV) is a positive strand RNA virus that propagates primarily in the liver. We show here that the liver‐specific microRNA‐122 (miR‐122), a member of a class of small cellular RNAs that mediate post‐transcriptional gene regulation usually by repressing the translation of mRNAs through interaction with their 3′‐untranslated regions (UTRs), stimulates the translation of HCV. Sequestration of miR‐122 in liver cell lines strongly reduces HCV translation, whereas addition of miR‐122 stimulates HCV translation in liver cell lines as well as in the non‐liver HeLa cells and in rabbit reticulocyte lysate. The stimulation is conferred by direct interaction of miR‐122 with two target sites in the 5′‐UTR of the HCV genome. With a replication‐defective NS5B polymerase mutant genome, we show that the translation stimulation is independent of viral RNA synthesis. miR‐122 stimulates HCV translation by enhancing the association of ribosomes with the viral RNA at an early initiation stage. In conclusion, the liver‐specific miR‐122 may contribute to HCV liver tropism at the level of translation.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c10803c29bf2f2df15974c9a249e14f3143450f5

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Citations in the corpus

Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation (2014, background): “The mechanism of the miR-122mediated stimulation of HCV gene expression is one of the rare cases and remains partially unsolved [108].”
MicroRNAs in development and disease. (2011, background): “Interestingly, two putative miR-122 targeting sites were discovered in the RNA genome of HCV; two in the 5= noncoding region (NCR) between the stem-loops I and II and one in the 3= NCR, which were highly conserved among six HCV genotypes (244, 284).”
Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties (2009, positive): “, 2008), and further studies have implicated miR-122 in HCV translation, suggesting the involvement of miR-122 in HCV tropism to the liver (Henke et al., 2008).”
Regulation of mRNA translation and stability by microRNAs. (2010, background): “(13) found that miR-122 may also stimulate HCV RNA translation, possibly by increasing ribosome loading on the HCV IRES.”