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.

Equipe labélisée Ligue Nationale Contre le Cancer Montpellier France

Institut de Génétique Humaine Montpellier France

Institut de Génétique Moléculaire de Montpellier University of Montpellier CNRS Montpellier France

Institut de Génomique Fonctionnelle University of Montpellier CNRS INSERM Montpellier France

Institute of Molecular Genetics Czech Academy of Sciences Prague Czech Republic

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Dynamic interaction of spliceosomal snRNPs with coilin explains Cajal body characteristics

Coilin and Cajal bodies

Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity