Wei, YiLee, NathanPan, LixiaDhakshnamoorthy, JothySun, Ling-lingZofall, MartinWheeler, DavidGrewal, Shiv2023-11-202021-02-11Wei, Yi, Nathan Lee, Lixia Pan, Jothy Dhakshnamoorthy, Ling-ling Sun, Martin Zofall, David Wheeler et al. "TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation." Nat Cell Biol 23, no. 3 (2021): 243-256. DOI: 10.1038/s41556-021-00631-y1465-73921476-4679https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37377415Cell proliferation and differentiation require signaling 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 signaling pathway reprograms gene expression patterns and contributes to diseases such as cancer.en-USCell BiologyJournal Article2023-11-2010.1038/s41556-021-00631-y