0488090 - ÚMG 2018 RIV US eng J - Journal Article
Malinová, Anna - Cvačková, Zuzana - Matějů, Daniel - Hořejší, Zuzana - Abeza, C. - Vandermoere, F. - Bertrand, E. - Staněk, David - Verheggen, C.
Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones.
Journal of Cell Biology. Roč. 216, č. 6 (2017), s. 1579-1596. ISSN 0021-9525. E-ISSN 1540-8140
R&D Projects: GA ČR GPP301/12/P425; GA ČR GA15-00790S; GA ČR(CZ) GA14-34264S; GA MŠMT LO1419
Institutional support: RVO:68378050
Keywords : dominant retinitis-pigmentosa * splicing factor prp8 * rna-polymerase-ii * structural basis * spliceosomal snrnps * coiled bodies * cajal bodies * r2tp complex * mutations * biogenesis
OECD category: Biochemistry and molecular biology
Impact factor: 8.784, year: 2017 ; AIS: 4.765, rok: 2017
DOI: https://doi.org/10.1083/jcb.201701165

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.
Permanent Link: http://hdl.handle.net/11104/0282716