PXD024747

PXD024747 is an original dataset announced via ProteomeXchange.

Title	Nonsense-mediated mRNA decay relies on "two-factor authentication" by SMG5-SMG7
Description	Eukaryotic gene expression is constantly regulated and controlled by the translation-coupled nonsense-mediated mRNA decay (NMD) pathway. Aberrant translation termination leads to NMD activation and robust clearance of NMD targets via two seemingly independent and redundant mRNA degradation branches. Here, we uncover that the loss of the first SMG5-SMG7-dependent pathway also inactivates the second SMG6-dependent branch, indicating an unexpected functional hierarchy of the final NMD steps. Transcriptome-wide analyses of SMG5-SMG7-depleted cells confirm complete NMD inhibition resulting in massive transcriptomic alterations. The NMD activity conferred by SMG5-SMG7 is determined to varying degrees by their interaction with the central NMD factor UPF1, heterodimer formation and the initiation of deadenylation. Surprisingly, we find that SMG5 functionally substitutes SMG7 and vice versa. Our data support an improved model for NMD execution that features two-factor authentication involving UPF1 phosphorylation and SMG5-SMG7 recruitment to access SMG6 activity.
HostingRepository	PRIDE
AnnounceDate	2021-05-08
AnnouncementXML	Submission_2021-07-19_23:19:12.584.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastian Kallabis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-15 08:26:56	ID requested
1	2021-05-08 02:35:49	announced
⏵ 2	2021-07-19 23:19:13	announced	2021-07-20: Updated publication reference for PubMed record(s): 34172724.

Boehm V, Kueckelmann S, Gerbracht JV, Kallabis S, Britto-Borges T, Altm, ü, ller J, Kr, ü, ger M, Dieterich C, Gehring NH, SMG5-SMG7 authorize nonsense-mediated mRNA decay by enabling SMG6 endonucleolytic activity. Nat Commun, 12(1):3965(2021) [pubmed]

submitter keyword: Nonsense-mediated mRNA decay, mRNA degradation, gene expression, UPF1, SMG5-SMG7, SMG6

Volker Boehm
contact affiliation	Institute for Genetics, University of Cologne, 50674 Cologne, Germany Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50937 Cologne, Germany
contact email	boehmv@uni-koeln.de
lab head
Sebastian Kallabis
contact affiliation	CECAD Research Center University of Cologne
contact email	skallab5@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/2021/05/PXD024747

PRIDE project URI

• PRIDE
  1. PXD024747
     1. Label: PRIDE project
     2. Name: Nonsense-mediated mRNA decay relies on "two-factor authentication" by SMG5-SMG7