PXD034007

PXD034007 is an original dataset announced via ProteomeXchange.

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	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:21.313.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manfred Heller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

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.

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]

submitter keyword: Driver gene

cancer

long non-coding RNAs

Rory Johnson
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
Manfred Heller
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

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

• PRIDE
  1. PXD034007
     1. Label: PRIDE project
     2. Name: Tumour mutations in long noncoding RNAs enhance cell fitness