RRC ID 64325
Author Wei Y, Lee NN, Pan L, Dhakshnamoorthy J, Sun LL, Zofall M, Wheeler D, Grewal SIS.
Title TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.
Journal Nat Cell Biol
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.
Volume 23(3)
Pages 243-256
Published 2021-3-1
DOI 10.1038/s41556-021-00631-y
PII 10.1038/s41556-021-00631-y
PMID 33574613
PMC PMC9260697
MeSH Cell Proliferation* Chromatin Assembly and Disassembly* Gene Expression Regulation, Fungal* Heterochromatin / genetics Heterochromatin / metabolism* Mitosis Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Phosphorylation Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism Proteolysis RNA Processing, Post-Transcriptional* Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces / growth & development Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Ubiquitination
IF 20.042