title: SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs.
abstract: Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here, we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing "cohesion fatigue". Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1-depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1- and PRPF8-depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer.
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: van der Lelij
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Roman R
authors.initials: RR
authors.lastname: Stocsits
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Rene
authors.initials: R
authors.lastname: Ladurner
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Petzold
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Kreidl
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria EMBL Heidelberg, Heidelberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Koch
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmitz
authors.affiliation: EMBL Heidelberg, Heidelberg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Neumann
authors.affiliation: EMBL Heidelberg, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Ellenberg
authors.affiliation: IMP Research Institute of Molecular Pathology, Vienna, Austria Jan-Michael.Peters@imp.ac.at.
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Peters
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D059467:Transcriptome / Q000502:physiology
chemical_list: C115681:APC2 protein, human; D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D056918:Nuclear Receptor Coactivators; D012322:RNA Precursors; C111791:SNW1 protein, human
keywords: cell cycle; mitosis; pre‐mRNA splicing; sister chromatid cohesion