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

Klára Klimešová (1) , Jitka Vojáčková (1) , Nenad Radivojević (1) , Franck Vandermoere (2) , Edouard Bertrand (3, 4) , Celine Verheggen (3, 4) , David Staněk (1)

1 IMG / CAS - Institute of Molecular Genetics of the Czech Academy of Sciences
2 IGF - Institut de Génomique Fonctionnelle
3 IGH - Institut de génétique humaine
4 IGMM - Institut de Génétique Moléculaire de Montpellier

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 regeneration 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.

Mots clés: RNA quality control; RNA splicing

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Klára Klimešová, Jitka Vojáčková, Nenad Radivojević, Franck Vandermoere, Edouard Bertrand, et al.. TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation. Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-23934-y⟩. ⟨hal-03413707⟩