PXD005189

PXD005189 is an original dataset announced via ProteomeXchange.

Title	DDX54 regulates transcriptome dynamics during DNA damage response, RBPome
Description	The cellular response to genotoxic stress is a well-characterized network of DNA surveillance pathways. The contribution of posttranscriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing irradiation (IR). Interestingly, more than 260 proteins showed increased binding to poly(A) RNA in IR-exposed cells and were comprised of many nucleolar proteins. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that DDX54 is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well defined class of pre-mRNAs which harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Since DDX54 promotes survival after exposure to IR its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR.
HostingRepository	PRIDE
AnnounceDate	2017-06-12
AnnouncementXML	Submission_2017-06-12_03:23:43.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Koshi Imami
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-19 02:03:50	ID requested
⏵ 1	2017-06-12 03:23:44	announced

Milek M, Imami K, Mukherjee N, Bortoli F, Zinnall U, Hazapis O, Trahan C, Oeffinger M, Heyd F, Ohler U, Selbach M, Landthaler M, DDX54 regulates transcriptome dynamics during DNA damage response. Genome Res, 27(8):1344-1359(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Human, RBPome, DNA damage, RBPome

Matthias Selbach
contact affiliation	Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association
contact email	matthias.selbach@mdc-berlin.de
lab head
Koshi Imami
contact affiliation	MDC
contact email	liqerume2000@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005189
     1. Label: PRIDE project
     2. Name: DDX54 regulates transcriptome dynamics during DNA damage response, RBPome