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

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. Wei et al. report that in yeast TOR suppresses gametogenic gene expression in mitosis by facilitating RNA decay and facultative heterochromatin assembly. During meiosis, TOR activity is downregulated to permit gametogenesis.

Automated summary

The study demonstrates that in fission yeast, Tor2 controls gene expression through RNA decay and facultative heterochromatin assembly, playing a critical role in sustaining cell proliferation. The dynamic nature of Tor2-mediated control of RNA elimination machinery defines gene expression patterns that coordinate fundamental chromosomal events.