MiR-122 does not modulate the elongation phase of hepatitis C virus RNA synthesis in isolated replicase complexes

Rodrigo A. Villanueva, Rohit K. Jangra, Min Kyung Yi, Richard Pyles, Nigel Bourne, Stanley M. Lemon

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

miR-122 is an abundant, liver-specific microRNA that is required for efficient amplification of hepatitis C virus (HCV) RNA. Recent studies with a miR-122-specific locked nucleic acid antagomir have shown it to be an important host target for therapeutic intervention. However, considerable controversy exists concerning the mechanisms underlying the dependence of HCV replication on miR-122. We studied the impact of miR-122 on the rate of [32P]-incorporation into positive-strand viral RNA by membrane-bound replicase complexes isolated from cells containing HCV RNA replicons. [32P]-incorporation in this cell-free system represents primarily the elongation phase of RNA synthesis, with little or no de novo initiation, and was not affected by the addition of either excess miR-122 or a miR-122-specific antisense oligonucleotide that suppresses replication in vivo. We also found no evidence that detectable quantities of miR-122 are specifically associated with replicase complexes in vivo. These results are consistent with miR-122 acting at an alternative step in the viral life cycle, promoting cap-independent viral translation, enhancing viral RNA stability, or facilitating de novo initiation of viral RNA synthesis.

Original languageEnglish (US)
Pages (from-to)119-123
Number of pages5
JournalAntiviral Research
Volume88
Issue number1
DOIs
StatePublished - Oct 2010

Fingerprint

Viral RNA
Hepacivirus
RNA
Replicon
Cell-Free System
Antisense Oligonucleotides
RNA Stability
Virus Replication
Life Cycle Stages
MicroRNAs
Membranes
Liver
Therapeutics

Keywords

  • Hepatitis C virus
  • MicroRNA
  • MiR-122
  • RNA replication

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

MiR-122 does not modulate the elongation phase of hepatitis C virus RNA synthesis in isolated replicase complexes. / Villanueva, Rodrigo A.; Jangra, Rohit K.; Yi, Min Kyung; Pyles, Richard; Bourne, Nigel; Lemon, Stanley M.

In: Antiviral Research, Vol. 88, No. 1, 10.2010, p. 119-123.

Research output: Contribution to journalArticle

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