Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis.

Published

Journal Article

Although inhibition of RNA interference (RNAi) by plant virus proteins has been shown to enhance viral replication and pathogenesis in plants, no viral gene product has as yet been shown to inhibit RNAi in vertebrate cells. Here, we present evidence demonstrating that the highly structured approximately 160-nucleotide adenoviral VA1 noncoding RNA can inhibit RNAi at physiological levels of expression. VA1, which is expressed at very high levels in adenovirus-infected cells, potently inhibited RNAi induced by short hairpin RNAs (shRNAs) or human microRNA precursors but did not affect RNAi induced by artificial short interfering RNA duplexes. Inhibition appeared to be due both to inhibition of nuclear export of shRNA or premicro-RNA precursors, competition for the Exportin 5 nuclear export factor, and inhibition of Dicer function by direct binding of Dicer. Together, these data argue that adenovirus infection can result in inhibition of RNAi and identify VA1 RNA as the first viral gene product able to inhibit RNAi in human cells.

Full Text

Duke Authors

Cited Authors

  • Lu, S; Cullen, BR

Published Date

  • December 2004

Published In

Volume / Issue

  • 78 / 23

Start / End Page

  • 12868 - 12876

PubMed ID

  • 15542639

Pubmed Central ID

  • 15542639

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/JVI.78.23.12868-12876.2004

Language

  • eng

Conference Location

  • United States