PXD001249

PXD001249 is an original dataset announced via ProteomeXchange.

Title	SNW1 is required for sister chromatid cohesion
Description	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.
HostingRepository	PRIDE
AnnounceDate	2016-06-29
AnnouncementXML	Submission_2016-06-29_09:10:11.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD001249
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Gerhard Duernberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deaminated residue; methylthiolated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2014-08-20 01:27:21	ID requested
⏵ 1	2016-06-29 09:10:12	announced

van der Lelij P, Stocsits RR, Ladurner R, Petzold G, Kreidl E, Koch B, Schmitz J, Neumann B, Ellenberg J, Peters JM, SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs. EMBO J, 33(22):2643-58(2014) [pubmed]

curator keyword: Biomedical

submitter keyword: SNW1, cell cycle, mitosis, pre-mRNA splicing, sister chromatid cohesion

Jan-Michael Peters
contact affiliation	IMP - Research Institute of Molecular Pathology, Austria
contact email	Jan-Michael.Peters@imp.ac.at
lab head
Gerhard Duernberger
contact affiliation	GMI/IMP/IMBA
contact email	gerhard.duernberger@imp.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001249
     1. Label: PRIDE project
     2. Name: SNW1 is required for sister chromatid cohesion