Condensation of ZFP207 and U1 SnRNP Promotes Spliceosome Assembly

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2025 Mar 6

PMID 40050462

Authors

Yuenan Zhou

Chong Tong

Zuokun Shi

Yan Zhang

Xushen Xiong

Xiaohua Shen

Xiaoyu Li

Yafei Yin

Affiliations

Soon will be listed here.

Abstract

The U1 small nuclear ribonucleoprotein (snRNP) has 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 zinc finger protein 207 (ZFP207) as a key regulator of U1 snRNP function that substantially promotes spliceosome assembly. Acute depletion of ZFP207 results in a series of molecular phenotypes indicative of U1 snRNP dysregulation. Mechanistically, the N-terminal zinc finger domains of ZFP207 directly bind to stem-loop 3 of U1 snRNA, while its C-terminal intrinsically disordered regions undergo phase separation to form 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 effective U1 snRNP function and promoting efficient spliceosome assembly.

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