ArticleNucleic acids research2022
The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 16 citations in OpenAlex.
- Selective and Potent First-in-Class CRBN-Dependent Molecular Glue Degraders of WW Domain-Binding Protein 4.Angewandte Chemie (International ed. in English) · 2026Article
- Neurochondrin promotes U5 snRNP maturation by regulating AAR2 release from PRPF8.Nucleic acids research · 2026Article
- Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.Molecular cell · 2024Article
- Illuminating the role of chaperones in spliceosome biogenesis and recycling.Nature structural & molecular biology · 2024Article
- Structural basis of human U5 snRNP late biogenesis and recycling.Nature structural & molecular biology · 2024Article
- Structure of the human 20S U5 snRNP.Nature structural & molecular biology · 2024Article
- Alternative splicing regulation by tumor suppressing subtransferable candidate 4: a pathway to tumor suppression.Frontiers in immunology · 2024Article
- The nuclear GYF protein CD2BP2/U5-52K is required for T cell homeostasis.Frontiers in immunology · 2024Article
- Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.American journal of human genetics · 2023Article
- Large-scale map of RNA binding protein interactomes across the mRNA life-cycle.bioRxiv : the preprint server for biology · 2023Article
- Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex.Nature communications · 2023Article
- Structural and functional investigation of the human snRNP assembly factor AAR2 in complex with the RNase H-like domain of PRPF8.Acta crystallographica. Section D, Structural biology · 2022Article
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8 authors at 3 institutions in 1 country.
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Abstract
Biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and their recycling after splicing require numerous assembly/recycling factors whose modes of action are often poorly understood. The intrinsically disordered TSSC4 protein has been identified as a nuclear-localized U5 snRNP and U4/U6-U5 tri-snRNP assembly/recycling factor, but how TSSC4's intrinsic disorder supports TSSC4 functions remains unknown. Using diverse interaction assays and cryogenic electron microscopy-based structural analysis, we show that TSSC4 employs four conserved, non-contiguous regions to bind the PRPF8 Jab1/MPN domain and the SNRNP200 helicase at functionally important sites. It thereby inhibits SNRNP200 helicase activity, spatially aligns the proteins, coordinates formation of a U5 sub-module and transiently blocks premature interaction of SNRNP200 with at least three other spliceosomal factors. Guided by the structure, we designed a TSSC4 variant that lacks stable binding to the PRPF8 Jab1/MPN domain or SNRNP200 in vitro. Comparative immunoprecipitation/mass spectrometry from HEK293 nuclear extract revealed distinct interaction profiles of wild type TSSC4 and the variant deficient in PRPF8/SNRNP200 binding with snRNP proteins, other spliceosomal proteins as well as snRNP assembly/recycling factors and chaperones. Our findings elucidate molecular strategies employed by an intrinsically disordered protein to promote snRNP assembly, and suggest multiple TSSC4-dependent stages during snRNP assembly/recycling.
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