Phosphorylation of SF3B1 by CDK11 orchestrates spliceosome activation via SNIP1-dependent RES complex recruitment - PubMed
3 hours ago
- #CDK11
- #spliceosome
- #SF3B1
- SF3B1, a spliceosome component, is phosphorylated by CDK11 during activation and stays phosphorylated in active spliceosomes.
- A CDK11 inhibitor arrests a spliceosome intermediate called BOTS964, which includes the NTR complex but not the NTC complex.
- Phosphorylated SF3B1 interacts with the U6 snRNA internal stem-loop, suggesting it helps stabilize the RNA catalytic core.
- The phosphorylation is recognized by SNIP1's FHA domain, promoting recruitment of the RES complex during spliceosome activation.
- Depleting SNIP1 disrupts RES incorporation, causes splicing defects, and leads to hyperphosphorylation of SF3B1 by CDK11.
- Mutations in SNIP1's FHA domain, like the neurodevelopmental disorder-linked E366G, impair binding, splicing, and cell viability.