Reference - PMID:33574613 - TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.
Reference summary
- PubMed ID
- PMID:33574613
- Title
- TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation.
- Authors
- Wei Y, Lee NN, Pan L, Dhakshnamoorthy J, Sun LL, Zofall M, Wheeler D, Grewal SIS
- Citation
- Nat Cell Biol 2021 Mar;23(3):243-256
- Publication year
- 2021
- 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.
Annotation
Multi-locus phenotype
Genes:
Genotypes:
- cul4delta tor2-ts6(S550P,K710M aa)
- ddb1delta tor2-ts6(S550P,K710M aa)
- mts2-1(unknown) tor2-ts6(S550P,K710M aa)
- pir1-S12D(S215D,S233D,S237D,S248D,S265D,S285D,S299D,S303D,S325D,S334D,S434D,S503D aa) tor2-ts6(S550P,K710M aa)
- pir1-SD(S285D aa) tor2-ts6(S550P,K710M aa)
Qualitative gene expression
Single locus phenotype
Genes:
Genotypes:
- pir1-S12A(S215A,S233A,S237A,S248A,S265A,S285A,S299A,S303A,S325A,S334A,S434A,S503A aa)