PXD024747 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD024747
- Label: PRIDE project
- Name: Nonsense-mediated mRNA decay relies on "two-factor authentication" by SMG5-SMG7