PXD027120

PXD027120 is an original dataset announced via ProteomeXchange.

Title	Deciphering the cellular roles and dissecting functional regions of UPF3A and UPF3B in human NMD
Description	The paralogous proteins UPF3A and UPF3B are involved in recognizing defective mRNAs that are degraded by nonsense-mediated mRNA decay (NMD). While UPF3B has been demonstrated to support NMD, UPF3A was reported to act either an NMD activator or an NMD inhibitor. Here, we present a comprehensive functional analysis of UPF3A and UPF3B in human cells using overexpression, knockdowns, knockouts (KO) and rescue experiments. Overexpression or knockout of UPF3A did not result in detectable changes in global NMD activity or other specific transcriptome alterations . NMD activity was also virtually unchanged in UPF3B KO cells. In contrast, the co-depletion or co-knockout of UPF3A and UPF3B resulted in a marked NMD inhibition and a global upregulation of PTC-containing transcripts. In rescue experiments UPF3B was fully functional when either UPF2- or EJC binding was impaired . However, the deletion of both interaction sites or one interaction site and a central region of UPF3B impaired its NMD function. Altogether, our work identifies critical functional domains of UPF3B and establishes redundant roles of UPF3A and UPF3B during NMD.
HostingRepository	PRIDE
AnnounceDate	2022-05-04
AnnouncementXML	Submission_2022-05-04_03:59:41.682.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Prerana Wagle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-05 21:40:29	ID requested
⏵ 1	2022-05-04 03:59:42	announced

Dataset with its publication pending

submitter keyword: Nonsense-mediated mRNA decay, gene paralogs, mRNA turnover, UPF3

Niels H. Gehring
contact affiliation	Institute for Genetics, UzK, Cologne, Germany
contact email	ngehring@uni-koeln.de
lab head
Prerana Wagle
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027120
     1. Label: PRIDE project
     2. Name: Deciphering the cellular roles and dissecting functional regions of UPF3A and UPF3B in human NMD