New roles for Dicer in the nucleolus and its relevance to cancer

Benjamin Roche1, Benoît Arcangioli2, Rob Martienssen1,3

  • 1a Martienssen Lab, Cold Spring Harbor Laboratory , Cold Spring Harbor , NY , USA.

Insights

The RNA interference pathway, including Dicer, plays a novel role in the nucleolus of quiescent yeast cells. This finding suggests a conserved function that may link DICER1 mutations to cancer predisposition in mammals.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The nucleolus is a nuclear compartment crucial for ribosome biogenesis.
  • Dysregulation of nucleolar function is linked to various cancers, involving tumor suppressors and proto-oncogenes.
  • These genes interact with RNA polymerase I transcription and nucleolar stress responses.

Purpose of the Study:

  • To investigate the role of the RNA interference (RNAi) pathway in the nucleolus.
  • To explore the function of Dicer within the nucleolus of quiescent yeast cells.
  • To determine if this nucleolar function is evolutionarily conserved.

Main Methods:

  • Utilized the fission yeast Schizosaccharomyces pombe as a model organism.
  • Investigated the RNA interference pathway components, specifically Dicer.
  • Focused on nucleolar functions distinct from pericentromeric silencing.

Main Results:

  • Identified an essential role for Dicer and the RNAi pathway in the nucleolus of quiescent S. pombe.
  • Demonstrated that this pathway controls RNA polymerase I release in the nucleolus.
  • This function is separate from its known role in pericentromeric silencing.

Conclusions:

  • The RNA interference pathway has a novel, conserved function within the nucleolus.
  • This nucleolar role of Dicer controls RNA polymerase I release.
  • DICER1 mutations may predispose to tumorigenesis in mammals due to this conserved function.

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