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PXD024747

PXD024747 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNonsense-mediated mRNA decay relies on "two-factor authentication" by SMG5-SMG7
DescriptionEukaryotic 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.
HostingRepositoryPRIDE
AnnounceDate2021-05-08
AnnouncementXMLSubmission_2021-07-19_23:19:12.584.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSebastian Kallabis
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-15 08:26:56ID requested
12021-05-08 02:35:49announced
22021-07-19 23:19:13announced2021-07-20: Updated publication reference for PubMed record(s): 34172724.
Publication List
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]
Keyword List
submitter keyword: Nonsense-mediated mRNA decay, mRNA degradation, gene expression, UPF1, SMG5-SMG7, SMG6
Contact List
Volker Boehm
contact affiliationInstitute for Genetics, University of Cologne, 50674 Cologne, Germany Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50937 Cologne, Germany
contact emailboehmv@uni-koeln.de
lab head
Sebastian Kallabis
contact affiliationCECAD Research Center University of Cologne
contact emailskallab5@uni-koeln.de
dataset submitter
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