TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation

Nat Cell Biol. 2021 Mar;23(3):243-256. doi: 10.1038/s41556-021-00631-y. Epub 2021 Feb 11.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Video-Audio Media

MeSH terms

  • 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

Substances

  • Heterochromatin
  • Schizosaccharomyces pombe Proteins
  • tor2 protein, S pombe
  • Proteasome Endopeptidase Complex