Evidence for a cytoplasmic microprocessor of pri-miRNAs

Jillian S. Shapiro, Ryan A. Langlois, Alissa M. Pham, Benjamin R. Tenoever

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

microRNAs (miRNAs) represent a class of noncoding RNAs that fine-tune gene expression through post-transcriptional silencing. While miRNA biogenesis occurs in a stepwise fashion, initiated by the nuclear microprocessor, rare noncanonical miRNAs have also been identified. Here we characterize the molecular components and unique attributes associated with the processing of virus-derived cytoplasmic primary miRNAs (c-pri-miRNAs). RNA in situ hybridization and inhibition of cellular division demonstrated a complete lack of nuclear involvement in c-pri-miRNA cleavage while genetic studies revealed that maturation still relied on the canonical nuclear RNase III enzyme, Drosha. The involvement of Drosha was mediated by a dramatic relocalization to the cytoplasm following virus infection. Deep sequencing analyses revealed that the cytoplasmic localization of Drosha does not impact the endogenous miRNA landscape during infection, despite allowing for robust synthesis of virus-derived miRNAs in the cytoplasm. Taken together, this research describes a unique function for Drosha in the processing of highly structured cytoplasmic RNAs in the context of virus infection.

Original languageEnglish (US)
Pages (from-to)1338-1346
Number of pages9
JournalRNA
Volume18
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • Argonaute
  • DGCR8
  • Drosha translocation
  • Virus

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