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Updated: Nov 17, 2025
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell
Yi Wei1, Nathan N Lee1,2, Lixia Pan1,3
1Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochromatin assembly. Phosphorylation by Tor2 protects Pir1 from degradation by the ubiquitin-proteasome system involving the polyubiquitin Ubi4 stress-response protein and the Cul4-Ddb1 E3 ligase. This pathway suppresses widespread and untimely gene expression and is critical for sustaining cell proliferation. Moreover, we find that the dynamic nature of Tor2-mediated control of RNA elimination machinery defines gene expression patterns that coordinate fundamental chromosomal events during gametogenesis, such as meiotic double-strand-break formation and chromosome segregation. These findings have important implications for understanding how the TOR signalling pathway reprogrammes gene expression patterns and contributes to diseases such as cancer.
Insights
The TORC1 complex’s Tor2 subunit controls gene expression by stabilizing the Pir1 protein, preventing widespread gene activation and ensuring cell proliferation. This mechanism is vital for chromosomal events during gametogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cellular processes like proliferation and differentiation depend on precise gene expression control.
- Signaling pathways are crucial for regulating timely gene expression.
Purpose of the Study:
- To investigate the role of Tor2, the catalytic subunit of TORC1, in regulating gene expression.
- To elucidate the mechanism by which Tor2 controls the nuclear RNA elimination network.
Main Methods:
- Investigated the interaction between Tor2 and the Pir1 protein.
- Analyzed the impact of Tor2 phosphorylation on Pir1 stability.
- Examined the role of the ubiquitin-proteasome system (Ubi4, Cul4-Ddb1) in Pir1 degradation.
- Studied the effects on gene expression, heterochromatin assembly, and gametogenesis.
Main Results:
- Tor2 phosphorylation protects Pir1 from degradation by the ubiquitin-proteasome system.
- This pathway suppresses untimely and widespread gene expression, crucial for cell proliferation.
- Tor2-mediated RNA elimination dynamically regulates gene expression patterns during gametogenesis, including meiotic events.
Conclusions:
- The TORC1 pathway, via Tor2 and Pir1, controls gene expression through RNA decay and heterochromatin formation.
- This regulation is essential for cell proliferation and coordinating chromosomal events in gametogenesis.
- Dysregulation of this pathway may contribute to diseases like cancer.
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