PXD034007-1
PXD034007 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Tumour mutations in long noncoding RNAs enhance cell fitness |
Description | Tumour DNA contains thousands of somatic single nucleotide variants (SNVs) in non-protein-coding elements, yet their functional significance remains poorly understood. Amongst the most highly mutated elements are long noncoding RNAs (lncRNAs), functional transcripts with known roles in carcinogenesis. To search for driver mutations in lncRNAs, we apply an integrative driver discovery algorithm to SNVs from 2583 primary tumours and 3527 metastases to reveal 54 potential “driver lncRNAs”. Our algorithm confirms a particularly high mutation rate in the iconic cancer lncRNA, NEAT1, which has been ascribed by recent studies to passenger effects. We directly test the functionality of NEAT1 SNVs using in cellulo mutagenesis, identifying discrete regions where mutations reproducibly increase cell proliferation in diverse cell backgrounds, both cancerous and normal. In particular, mutations in the 5’ region alter ribonucleoprotein assembly and boost the population of subnuclear paraspeckles, thus mechanistically linking mutations to cellular proliferation. We then used RNA-pull down followed by mass spectrometry to identify the protein interactor changing between the wild type and mutant form of NEAT1. |
HostingRepository | PRIDE |
AnnounceDate | 2023-07-20 |
AnnouncementXML | Submission_2023-07-20_10:37:31.335.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | ManfredHeller |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-05-20 10:22:17 | ID requested | |
⏵ 1 | 2023-07-20 10:37:32 | announced | |
2 | 2023-11-14 09:02:27 | announced | 2023-11-14: Updated project metadata. |
Publication List
Esposito R, Lanz, ó, s A, Uroda T, Ramnarayanan S, B, ü, chi I, Polidori T, Guillen-Ramirez H, Mihaljevic A, Merlin BM, Mela L, Zoni E, Hovhannisyan L, McCluggage F, Medo M, Basile G, Meise DF, Zwyssig S, Wenger C, Schwarz K, Vancura A, Bosch-Guiteras N, Andrades Á, Tham AM, Roemmele M, Medina PP, Ochsenbein AF, Riether C, Kruithof-de Julio M, Zimmer Y, Medov, á M, Stroka D, Fox A, Johnson R, Tumour mutations in long noncoding RNAs enhance cell fitness. Nat Commun, 14(1):3342(2023) [pubmed] |
Keyword List
submitter keyword: Driver gene |
cancer |
long non-coding RNAs |
Contact List
RoryJohnson | |
---|---|
contact affiliation | 1.Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland. 2.Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland. 3. Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin D04 V1W8, Ireland. |
contact email | rory.johnson@ucd.ie |
lab head | |
ManfredHeller | |
contact affiliation | Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland |
contact email | pmscf@dbmr.unibe.ch |
dataset submitter |
Full Dataset Link List
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/2023/07/PXD034007 |
PRIDE project URI |
Repository Record List
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