microRNA-122 stimulates translation of hepatitis C virus RNA.
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.
Henke
Jura Inga
JI
Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
Goergen
Dagmar
D
Zheng
Junfeng
J
Song
Yutong
Y
Schüttler
Christian G
CG
Fehr
Carmen
C
Jünemann
Christiane
C
Niepmann
Michael
M
D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis*
C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins