Person: Lee, Nathan
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Lee, Nathan
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Publication TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation(Springer Science and Business Media LLC, 2021-02-11) Wei, Yi; Lee, Nathan; Pan, Lixia; Dhakshnamoorthy, Jothy; Sun, Ling-ling; Zofall, Martin; Wheeler, David; Grewal, ShivCell 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.