ZFP207 interacts with U1 snRNP to promote spliceosome assembly via phase separation [SNRNP70_AID_4sU]

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 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). The coordination between the N-terminus and C-terminus of ZFP207 drives the formation of biomolecular condensate with U1 snRNP, which creates a molecular environment to promote spliceosome assembly by facilitating the interactions between U1 snRNP and other splicing regulators. Collectively, our study demonstrates the critical role of ZFP207-mediated phase separation in ensuring proper U1 snRNP function and spliceosome assembly. To compare the function of ZFP207 with SNRNP70 in the regulation of U1 snRNP function, we established SNRNP70AID mESCs cell lines in which SNRNP70 degradation. We then performed gene expression profiling analysis using data obtained from RNA-seq of two independent replicates in control and SNRNP70AID group. Comparative gene expression profiling analysis of RNA-seq data of control and ZFP207AID group.