TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation

• Published in: Nature communications Vol. 12; no. 1; pp. 3646 - 15
• Main Authors: Klimešová, Klára, Vojáčková, Jitka, Radivojević, Nenad, Vandermoere, Franck, Bertrand, Edouard, Verheggen, Celine, Staněk, David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/109; 13/89; 14/32; 14/35; 14/63; 38/77; 631/337/1645/1769; 631/337/1645/1792; 82/58; Assembly; Biochemistry, Molecular Biology; Biosynthesis; Chaperones; Genomics; Humanities and Social Sciences; Life Sciences; multidisciplinary; Proteins; Recycling; Ribonucleoproteins (small nuclear); Science; Science (multidisciplinary); Splicing; RNA quality control; RNA splicing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23934-y

U5 snRNP is a complex particle essential for RNA splicing. U5 snRNPs undergo intricate biogenesis that ensures that only a fully mature particle assembles into a splicing competent U4/U6•U5 tri-snRNP and enters the splicing reaction. During splicing, U5 snRNP is substantially rearranged and leaves as a U5/PRPF19 post-splicing particle, which requires re-generation before the next round of splicing. Here, we show that a previously uncharacterized protein TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation. We provide evidence that TSSC4 associates with U5 snRNP chaperones, U5 snRNP and the U5/PRPF19 particle. Specifically, TSSC4 interacts with U5-specific proteins PRPF8, EFTUD2 and SNRNP200. We also identified TSSC4 domains critical for the interaction with U5 snRNP and the PRPF19 complex, as well as for TSSC4 function in tri-snRNP assembly. TSSC4 emerges as a specific chaperone that acts in U5 snRNP de novo biogenesis as well as post-splicing recycling. The correct assembly and recycling of the multicomponent spliceosome remains largely elusive. Here, the authors show that a previously uncharacterized protein TSSC4 associates with de novo formed spliceosomal U5 snRNP as well as with a post-splicing U5-PRPF19 particle, and that TSSC4 is important for assembly of the splicing competent tri-snRNP.