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Published on: May 30, 2025
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.
Abstract:
The nucleolus is a distinct compartment of the nucleus responsible for ribosome biogenesis. Mis-regulation of nucleolar functions and of the cellular translation machinery has been associated with disease, in particular with many types of cancer. Indeed, many tumor suppressors (p53, Rb, PTEN, PICT1, BRCA1) and proto-oncogenes (MYC, NPM) play a direct role in the nucleolus, and interact with the RNA polymerase I transcription machinery and the nucleolar stress response. We have identified Dicer and the RNA interference pathway as having an essential role in the nucleolus of quiescent Schizosaccharomyces pombe cells, distinct from pericentromeric silencing, by controlling RNA polymerase I release. We propose that this novel function is evolutionarily conserved and may contribute to the tumorigenic pre-disposition of DICER1 mutations in mammals.
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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