title: UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells.
abstract: UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation.
authors.affiliation: Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Varmark
authors.affiliation: Bioinformatics Centre, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Vitting-Seerup
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark Institute of Molecular Biology (IMB), Mainz, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Beli
authors.affiliation: Bioinformatics Centre, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Johannes
authors.initials: J
authors.lastname: Waage
authors.affiliation: Department of Cell Death and Metabolism, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Hakobyan
authors.affiliation: Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Mistrik
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Chunaram
authors.initials: C
authors.lastname: Choudhary
authors.affiliation: Department of Cell Death and Metabolism, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Bekker-Jensen
authors.affiliation: Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research University of Copenhagen, Copenhagen, Denmark niels.mailand@cpr.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Mailand
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002842:Chromatids / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017381:Spliceosomes / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D018797:Cell Cycle Proteins; D005136:Eye Proteins; D012322:RNA Precursors; D029701:Saccharomyces cerevisiae Proteins; C429294:UBL5 protein, human; D014452:Ubiquitins; D008025:Ligases; C452202:HUB1 protein, S cerevisiae
keywords: UBL5; pre‐mRNA splicing; sister chromatid cohesion; sororin; ubiquitin‐like protein
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