PXD022616 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Phosphoproteomics of C.elegans RNA binding protein mutants |
Description | Nonsense-mediated mRNA decay (NMD) monitors the quality of transcriptomes and degrades messenger RNAs containing splicing errors or premature stop codons. NMD thus dictates the severity and outcome of genetic disorders, gene edits and knockouts as well as the prevalence of neoantigens. Central to the NMD pathway are SMG-1, an ATM/ATR-like kinase, and its downstream target SMG-2/UPF1, a highly processive DNA/RNA helicase. Interestingly, many NMD factors acquired additional ‘moonlighting’ functions in the nucleus, including roles in DNA synthesis and DNA damage signalling. While having the same protein controlling RNA and DNA metabolism could be beneficial, it could also lead to signalling conflicts that jeopardize genome stability. Surprisingly little is known about the incidence and impact of such crosstalk in biology, neither in physiological nor in pathological scenarios. Here, via genetics screens and genome-wide analyses, we identified unforeseen crosstalk between RNA surveillance and DNA repair in living animals. Defects in RNA processing, due to viable THO complex or PNN-1 mutations, trigger SMG-1 activity, which causes a major shift in DNA repair and compromises genome stability in somatic tissues. Mechanistically, we find SMG-1 and SMG-2/UPF1, but not NMD per se, to suppress DNA repair by classical non-homologous end-joining while allowing mutagenic repair by single strand annealing. We postulate that aberrant RNA structures trigger crosstalk that re-directs DNA repair and genome evolution. |
HostingRepository | PRIDE |
AnnounceDate | 2022-08-12 |
AnnouncementXML | Submission_2022-08-11_22:12:48.594.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Juliette Kamp |
SpeciesList | scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-11-19 03:31:16 | ID requested | |
⏵ 1 | 2022-08-11 22:12:49 | announced | |
Publication List
Kamp JA, Lemmens BBLG, Romeijn RJ, Gonz, á, lez-Prieto R, Olsen JV, Vertegaal ACO, van Schendel R, Tijsterman M, THO complex deficiency impairs DNA double-strand break repair via the RNA surveillance kinase SMG-1. Nucleic Acids Res, 50(11):6235-6250(2022) [pubmed] |
Keyword List
submitter keyword: C.elegans |
Contact List
Marcel Tijsterman |
contact affiliation | Department of Human Genetics, Leiden University Medical Center, The Netherlands |
contact email | m.tijsterman@lumc.nl |
lab head | |
Juliette Kamp |
contact affiliation | Leiden University Medical Center |
contact email | j.a.kamp@lumc.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022616
- Label: PRIDE project
- Name: Phosphoproteomics of C.elegans RNA binding protein mutants