PXD019161

PXD019161 is an original dataset announced via ProteomeXchange.

Title	The exon junction complex component CASC3 is a major effector of nonsense-mediated mRNA decay in human cells
Description	In metazoans, the exon junction complex (EJC) is a central component of spliced messenger ribonucleoprotein particles (mRNPs). CASC3 has been reported to be a core component of the EJC and to be crucial for assembly, the splicing regulating function of the EJC and nonsense-mediated mRNA decay (NMD). However, recent evidence suggests that CASC3 functions differently from other EJC core components. To elucidate the cellular role of CASC3, we have established human cell lines in which CASC3 was inactivated by means of CRISPR-Cas9 genome editing. We show that in these cells CASC3 is dispensable for the splicing regulatory role of the EJC. However, we find that CASC3 depletion results in the upregulation of many known and novel NMD substrates, suggesting that CASC3 is required for the efficient execution of EJC-dependent NMD. Taken together, our results challenge the model of CASC3 as an assembly factor and core component of the EJC. Our data rather show that CASC3 is involved in the degradation of NMD substrates and therefore uncover the primary molecular function of CASC3 in human cells.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-08_18:34:50.555.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Janica Wiederstein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-13 04:59:01	ID requested
⏵ 1	2021-09-08 18:34:51	announced

Gerbracht JV, Boehm V, Britto-Borges T, Kallabis S, Wiederstein JL, Ciriello S, Aschemeier DU, Kr, ü, ger M, Frese CK, Altm, ü, ller J, Dieterich C, Gehring NH, CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex. Nucleic Acids Res, 48(15):8626-8644(2020) [pubmed]

submitter keyword: non-sense mediated mRNA decay, NMD, Exon junction complex (EJC)

Niels H. Gehring
contact affiliation	Institute for Genetics, University of Cologne, 50674 Cologne, Germany
contact email	ngehring@uni-koeln.de
lab head
Janica Wiederstein
contact affiliation	Institute for Genetics/CECAD (AG Krüger)
contact email	jwieders@uni-koeln.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD019161

PRIDE project URI

• PRIDE
  1. PXD019161
     1. Label: PRIDE project
     2. Name: The exon junction complex component CASC3 is a major effector of nonsense-mediated mRNA decay in human cells