PXD023942

PXD023942 is an original dataset announced via ProteomeXchange.

Title	SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes
Description	Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome––the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal subcomplexes such as SF3B1 and the large splicing cofactor SON but also with PRPFs and snRNAs related to the tri-snRNP complex. SANS is required for the transfer of tri-snRNPs between Cajal bodies and nuclear speckles for spliceosome assembly and may also participate in snRNP recycling back to Cajal bodies. SANS depletion alters the kinetics of spliceosome assembly, leading to accumulation of complex A. SANS deficiency and USH1G pathogenic mutations affects splicing of genes related to cell proliferation and USH. Thus, we provide the first evidence that splicing dysregulation may participate in the pathophysiology of Usher syndrome.
HostingRepository	PRIDE
AnnounceDate	2021-05-26
AnnouncementXML	Submission_2021-05-25_22:15:56.626.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Iwan Parfentev
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-02 04:31:12	ID requested
1	2021-05-25 07:37:05	announced
⏵ 2	2021-05-25 22:15:57	announced	2021-05-26: Updated project metadata.

10.1093/NAR/GKAB386;

Yildirim A, Mozaffari-Jovin S, Wallisch AK, Sch, ä, fer J, Ludwig SEJ, Urlaub H, L, ü, hrmann R, Wolfrum U, SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes. Nucleic Acids Res, 49(10):5845-5866(2021) [pubmed]

submitter keyword: intra-nuclear transport, Cajal bodies, ciliopathy, spliceosome, nuclear speckles, alternative splicing,Usher Syndrome

Henning Urlaub
contact affiliation	Bioanalytical Mass Spectrometry, Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany
contact email	henning.urlaub@mpibpc.mpg.de
lab head
Iwan Parfentev
contact affiliation	Max-Planck-Institute for Biophysical Chemistry
contact email	iwan.parfentev@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023942
     1. Label: PRIDE project
     2. Name: SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes