Discrete clusters of virus-encoded MicroRNAs are associated with complementary strands of the genome and the 7.2-kilobase stable intron in murine cytomegalovirus

Amy H. Buck, Javier Santoyo-Lopez, Kevin A. Robertson, Diwakar S. Kumar, Martin Reczko, Peter Ghazal

Research output: Contribution to journalArticlepeer-review

Abstract

The prevalence and importance of microRNAs (miRNAs) in viral infection are increasingly relevant. Eleven miRNAs were previously identified in human cytomegalovirus (HCMV); however, miRNA content in murine CMV (MCMV), which serves as an important in vivo model for CMV infection, has not previously been examined. We have cloned and characterized 17 novel miRNAs that originate from at least 12 precursor miRNAs in MCMV and are not homologous to HCMV miRNAs. In parallel, we applied a computational analysis, using a support vector machine approach, to identify potential precursor miRNAs in MCMV. Four of the top 10 predicted precursor sequences were cloned in this stuffy, and the combination of computational and cloning analysis demonstrates that MCMV has the capacity to encode miRNAs clustered throughout the genome. On the basis of drug sensitivity experiments for resolving the kinetic class of expression, we show that the MCMV miRNAs are both early and late gene products. Notably, the MCMV miRNAs occur on complementary strands of the genome in specific regions, a feature which has not previously been observed for viral miRNAs. One cluster of miRNAs occurs in close proximity to the 5' splice site of the previously identified 7.2-kb stable intron, implying a variety of potential regulatory mechanisms for MCMV miRNAs.

Original languageEnglish
Pages (from-to)13761-13770
Number of pages10
JournalJournal of Virology
Volume81
Issue number24
DOIs
Publication statusPublished - Dec 2007

Keywords

  • CAENORHABDITIS-ELEGANS/
  • VIRAL-INFECTION
  • GENE-EXPRESSION
  • MESSENGER-RNA
  • IDENTIFICATION
  • SEQUENCE
  • PATHOGENESIS
  • SYSTEM
  • FAMILY
  • GROWTH

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