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Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones
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SYSNO ASEP 0488090 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones Author(s) Malinová, Anna (UMG-J)
Cvačková, Zuzana (UMG-J) RID
Matějů, Daniel (UMG-J)
Hořejší, Zuzana (UMG-J) RID
Abeza, C. (FR)
Vandermoere, F. (FR)
Bertrand, E. (FR)
Staněk, David (UMG-J) RID
Verheggen, C. (FR)Number of authors 9 Source Title Journal of Cell Biology. - : Rockefeller University Press - ISSN 0021-9525
Roč. 216, č. 6 (2017), s. 1579-1596Number of pages 18 s. Language eng - English Country US - United States Keywords dominant retinitis-pigmentosa ; splicing factor prp8 ; rna-polymerase-ii ; structural basis ; spliceosomal snrnps ; coiled bodies ; cajal bodies ; r2tp complex ; mutations ; biogenesis Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GPP301/12/P425 GA ČR - Czech Science Foundation (CSF) GA15-00790S GA ČR - Czech Science Foundation (CSF) GA14-34264S GA ČR - Czech Science Foundation (CSF) LO1419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000402702500013 DOI https://doi.org/10.1083/jcb.201701165 Annotation Splicing is catalyzed by the spliceosome, a complex of five major small nuclear ribonucleoprotein particles (snRNPs). The pre-mRNA splicing factor PRPF8 is a crucial component of the U5 snRNP, and together with EFT UD2 and SNR NP200, it forms a central module of the spliceosome. Using quantitative proteomics, we identified assembly intermediates containing PRPF8, EFT UD2, and SNR NP200 in association with the HSP90/R2TP complex, its ZNH IT2 cofactor, and additional proteins. HSP90 and R2TP bind unassembled U5 proteins in the cytoplasm, stabilize them, and promote the formation of the U5 snRNP. We further found that PRPF8 mutants causing Retinitis pigmentosa assemble less efficiently with the U5 snRNP and bind more strongly to R2TP, with one mutant retained in the cytoplasm in an R2TP-dependent manner. We propose that the HSP90/R2TP chaperone system promotes the assembly of a key module of U5 snRNP while assuring the quality control of PRPF8. The proteomics data further reveal new interactions between R2TP and the tuberous sclerosis complex (TSC), pointing to a potential link between growth signals and the assembly of key cellular machines. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2018
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