Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones
Copyright policy )Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones
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 EFTUD2 and SNRNP200, it forms a central module of the spliceosome. Using quantitative proteomics, we identified assembly intermediates containing PRPF8, EFTUD2, and SNRNP200 in association with the HSP90/R2TP complex, its ZNHIT2 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.
- Institute of Molecular Genetics Czech Republic
- Université de Montpellier France
- Université de Montpellier (EPE) France
- French National Centre for Scientific Research France
- Charles University Czech Republic
Proteomics, rna-polymerase-ii, cajal bodies, Ribonucleoprotein, U4-U6 Small Nuclear, RNA Splicing, r2tp complex, Ribonucleoprotein, U1 Small Nuclear, RNA Precursors, Humans, Protein Interaction Domains and Motifs, HSP90 Heat-Shock Proteins, RNA, Messenger, spliceosomal snrnps, Research Articles, Ribonucleoprotein, U5 Small Nuclear, Protein Stability, Calcium-Binding Proteins, RNA-Binding Proteins, structural basis, splicing factor prp8, mutations, biogenesis, Peptide Elongation Factors, [SDV] Life Sciences [q-bio], coiled bodies, Multiprotein Complexes, Mutation, dominant retinitis-pigmentosa, RNA Interference, Retinitis Pigmentosa, HeLa Cells, Protein Binding
Proteomics, rna-polymerase-ii, cajal bodies, Ribonucleoprotein, U4-U6 Small Nuclear, RNA Splicing, r2tp complex, Ribonucleoprotein, U1 Small Nuclear, RNA Precursors, Humans, Protein Interaction Domains and Motifs, HSP90 Heat-Shock Proteins, RNA, Messenger, spliceosomal snrnps, Research Articles, Ribonucleoprotein, U5 Small Nuclear, Protein Stability, Calcium-Binding Proteins, RNA-Binding Proteins, structural basis, splicing factor prp8, mutations, biogenesis, Peptide Elongation Factors, [SDV] Life Sciences [q-bio], coiled bodies, Multiprotein Complexes, Mutation, dominant retinitis-pigmentosa, RNA Interference, Retinitis Pigmentosa, HeLa Cells, Protein Binding
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).86 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!