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Evidence for a cytoplasmic microprocessor of pri-miRNAs

Jillian S Shapiro1, Ryan A Langlois, Alissa M Pham

  • 1Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.

RNA (New York, N.Y.)
|May 29, 2012
PubMed

Insights

Virus infection triggers Drosha enzyme relocation to the cytoplasm, enabling the processing of viral microRNAs (miRNAs) without affecting host miRNAs. This reveals a novel cytoplasmic function for Drosha in viral RNA processing.

Area of Science:

  • Molecular Biology
  • Virology
  • RNA Biology

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression via post-transcriptional silencing.
  • Canonical miRNA biogenesis initiates in the nucleus with the microprocessor complex.
  • Noncanonical miRNA biogenesis pathways, including cytoplasmic processing, are less understood.

Purpose of the Study:

  • To characterize the molecular mechanisms and components involved in processing virus-derived cytoplasmic primary miRNAs (c-pri-miRNAs).
  • To investigate the role of Drosha, a nuclear RNase III enzyme, in cytoplasmic miRNA processing during viral infection.

Main Methods:

  • RNA in situ hybridization to visualize RNA localization.
  • Inhibition of cellular division to assess nuclear involvement.
  • Genetic studies to determine enzyme dependencies.
  • Deep sequencing to analyze miRNA profiles.

Main Results:

  • Virus infection induced Drosha relocalization from the nucleus to the cytoplasm.
  • c-pri-miRNA processing occurred independently of nuclear involvement but required Drosha.
  • Cytoplasmic Drosha facilitated robust viral miRNA synthesis without altering endogenous miRNA levels.

Conclusions:

  • Drosha exhibits a novel cytoplasmic function in processing viral-derived, highly structured RNAs during infection.
  • This noncanonical pathway allows for efficient viral miRNA production in the cytoplasm.

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