title: USP15 regulates dynamic protein-protein interactions of the spliceosome through deubiquitination of PRP31.
abstract: Post-translational modifications contribute to the spliceosome dynamics by facilitating the physical rearrangements of the spliceosome. Here, we report USP15, a deubiquitinating enzyme, as a regulator of protein-protein interactions for the spliceosome dynamics. We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3. The ubiquitination and deubiquitination status of PRP31 regulates its interaction with the U5 snRNP component PRP8, which is required for the efficient splicing of chromosome segregation related genes, probably by stabilizing the U4/U6.U5 tri-snRNP complex. Collectively, our data suggest that USP15 plays a key role in the regulation of dynamic protein-protein interactions of the spliceosome.
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea.
authors.forename: Tanuza
authors.initials: T
authors.lastname: Das
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu 02792, Seoul, Korea.
authors.forename: Joon Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu 02792, Seoul, Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.|Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rape
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu 02792, Seoul, Korea.
authors.forename: Eunice EunKyeong
authors.initials: EE
authors.lastname: Kim
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Song
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D000072260:RNA Splicing Factors / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics; D017381:Spliceosomes / Q000235:genetics; D064570:Ubiquitin-Specific Proteases / Q000235:genetics*; D054875:Ubiquitination / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C108507:PRPF3 protein, human; C115374:PRPF8 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; C416530:SART3 protein, human; C579226:USP15 protein, human; D064570:Ubiquitin-Specific Proteases; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human