PXD015158

PXD015158 is an original dataset announced via ProteomeXchange.

Title	Integrator restraints paraspeckles assembly by promoting the 3’-end processing of the polyadenylated lncRNA NEAT1_1
Description	Alternative 3’-end RNA processing provides an important source of transcriptome diversification, which impacts various biological processes and the etiology of diseases, including cancer. Here, we focused on a transcript isoform switch that leads to the readthrough expression of the long noncoding RNA NEAT1_2, at the expense of the shorter polyadenylated transcript NEAT1_1. Expression of NEAT1_2 is required for the formation of paraspeckles (PS), nuclear bodies that protect cancer cells from oncogene-induced replication stress and chemotherapy. Searching for proteins that interact with endogenous NEAT1 by RNA Affinity Purification coupled to mass spectrometry (RAP-MS), we identified factors involved in the 3’-end processing of polyadenylated (pA+) RNA as well as several components of the Integrator complex, known to process the 3’-ends of RNAs lacking polyadenylation sites. Unexpectedly, genetic perturbation experiments established that Integrator restraints NEAT1_2 expression, and thereby PS assembly, by promoting the 3’-end processing of pA+ NEAT1_1. Consistently, low expression levels of several Integrator subunits correlated with poorer prognosis of cancer patients exposed to chemotherapeutics. Our study identifies Integrator as a key regulator of PS biogenesis and highlights a previously unrecognized ability of the complex to process pA+ RNA. The data also establish a link between Integrator, cancer biology and chemosensitivity, which may be exploited therapeutically.
HostingRepository	PRIDE
AnnounceDate	2020-10-14
AnnouncementXML	Submission_2020-10-13_23:00:25.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Impens Francis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-27 03:50:07	ID requested
⏵ 1	2020-10-13 23:00:26	announced

Barra J, Gaidosh GS, Blumenthal E, Beckedorff F, Tayari MM, Kirstein N, Karakach TK, Jensen TH, Impens F, Gevaert K, Leucci E, Shiekhattar R, Marine JC, . Sci Adv, 6(27):eaaz9072(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: NEAT1

alternative 3’-end RNA processing, Integrator, Paraspeckles, cancer

Jean-Christophe Marine
contact affiliation	Laboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory for Molecular Cancer Biology, Department of Oncology, KULeuven, Leuven, Belgium
contact email	jeanchristophe.marine@kuleuven.vib.be
lab head
Impens Francis
contact affiliation	VIB Proteomics Core Ghent University
contact email	francis.impens@vib-ugent.be
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/2020/10/PXD015158

PRIDE project URI

• PRIDE
  1. PXD015158
     1. Label: PRIDE project
     2. Name: Integrator restraints paraspeckles assembly by promoting the 3’-end processing of the polyadenylated lncRNA NEAT1_1