Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA.
MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interaction between miR-122 and the 5' noncoding region of the viral genome was revealed by mutational analyses of the predicted microRNA binding site and ectopic expression of miR-122 molecules containing compensatory mutations. Studies with replication-defective RNAs suggested that miR-122 did not detectably affect mRNA translation or RNA stability. Therefore, miR-122 is likely to facilitate replication of the viral RNA, suggesting that miR-122 may present a target for antiviral intervention.
Jopling
Catherine L
CL
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Yi
Minkyung
M
Lancaster
Alissa M
AM
Lemon
Stanley M
SM
Sarnow
Peter
P
D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral