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Condensation of ZFP207 and U1 snRNP promotes spliceosome assembly [RAP-seq]

GSE275020 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2024/12/30 Platform GPL28330
Summary
U1 snRNP plays an essential role in initiating spliceosome assembly, yet the mechanism underlying its synergy with other splicing regulators for efficient spliceosome assembly remains elusive. Here we identify ZFP207 as a key regulator of U1 snRNP function that substantially promotes spliceosome assembly. Acute depletion of ZFP207 largely recapitulates the molecular phenotypes observed with the depletion of SNRNP70, a core component of U1 snRNP. Mechanistically, the N-terminal zinc finger domains of ZFP207 directly bind to U1 snRNA, while its C-terminus undergoes phase separation via intrinsically disordered regions (IDRs) to forms biomolecular condensates with U1 snRNP. These condensates create a crowded molecular environment that increases the local concentration of splicing snRNPs and regulators, thereby accelerating the speed of spliceosome assembly by facilitating interactions between U1 snRNP and other snRNPs. Collectively, our study demonstrates the critical role of phase separation in ensuring proper U1 snRNP function and efficient spliceosome assembly.
Published in
Condensation of ZFP207 and U1 snRNP promotes spliceosome assembly
Zhou Y, Tong C, Shi Z et al. · Nature structural & molecular biology 2025 · PMID 40050462 · doi:10.1038/s41594-025-01501-z
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Also filed as BioProject PRJNA1148976 and SRA study SRP526865. Searching any of these in the dataset finder brings you back here.

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