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Science 2 September 2005:
Vol. 309. no. 5740, pp. 1577 - 1581
DOI: 10.1126/science.1113329
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Reports

Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA

Catherine L. Jopling,1 MinKyung Yi,2 Alissa M. Lancaster,1 Stanley M. Lemon,2 Peter Sarnow1*

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.

1 Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
2 Center for Hepatitis Research, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019, USA.

* To whom correspondence should be addressed. E-mail: psarnow{at}stanford.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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K.-S. Chang, Z. Cai, C. Zhang, G. C. Sen, B. R. G. Williams, and G. Luo (2006)
J. Virol. 80, 7364-7374
   Abstract »    Full Text »    PDF »
A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA).
M. Castoldi, S. Schmidt, V. Benes, M. Noerholm, A. E. Kulozik, M. W. Hentze, and M. U. Muckenthaler (2006)
RNA 12, 913-920
   Abstract »    Full Text »    PDF »
Control of translation and mRNA degradation by miRNAs and siRNAs..
M. A. Valencia-Sanchez, J. Liu, G. J. Hannon, and R. Parker (2006)
Genes & Dev. 20, 515-524
   Abstract »    Full Text »    PDF »
Positive and Negative Modulation of Viral and Cellular mRNAs by Liver-specific MicroRNA miR-122.
C.L. JOPLING, K.L. NORMAN, and P. SARNOW (2006)
Cold Spring Harb Symp Quant Biol 71, 369-376
   Abstract »    PDF »
The Expanding Universe of Noncoding RNAs.
G.J. HANNON, F.V. RIVAS, E.P. MURCHISON, and J.A. STEITZ (2006)
Cold Spring Harb Symp Quant Biol 71, 551-564
   Abstract »    PDF »
Improved targeting of miRNA with antisense oligonucleotides..
S. Davis, B. Lollo, S. Freier, and C. Esau (2006)
Nucleic Acids Res. 34, 2294-2304
   Abstract »    Full Text »    PDF »
MicroRNA function: Multiple mechanisms for a tiny RNA?.
R. S. PILLAI (2005)
RNA 11, 1753-1761
   Abstract »    Full Text »    PDF »
MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function.
D. T. Humphreys, B. J. Westman, D. I. K. Martin, and T. Preiss (2005)
PNAS 102, 16961-16966
   Abstract »    Full Text »    PDF »
Ribo-gnome: The Big World of Small RNAs.
P. D. Zamore and B. Haley (2005)
Science 309, 1519-1524
   Abstract »    Full Text »    PDF »


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