PXD029592

PXD029592 is an original dataset announced via ProteomeXchange.

Title	Poly(A) RNA interactome capture upon HDAC inhibition by Romidepsin
Description	Immediate early genes (IEGs) represent a unique class of genes with rapid induction kinetics and transient expression patterns, which requires IEG mRNAs to be short-lived. Here, we establish cytoplasmic polyadenylation element-binding protein 4 (CPEB4) as a major determinant of IEG mRNA instability. We identified human CPEB4 as an RNA-binding protein (RBP) with enhanced association to poly(A) RNA upon inhibition of class I histone deacetylases (HDACs), which is known to cause widespread degradation of poly(A)-containing mRNA. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis using endogenously tagged CBEP4 in HeLa cells revealed that CPEB4 preferentially binds to the 3' untranslated region (UTR) of IEG mRNAs, at U-rich sequence motifs located in close proximity to the poly(A) site. By transcriptome-wide mRNA decay measurements, we found that the strength of CPEB4 binding correlates with short mRNA half-lives, and that loss of CPEB4 expression leads to the stabilization of IEG mRNAs. Further, we demonstrate that CPEB4 mediates mRNA degradation by recruitment of the evolutionarily conserved CCR4-NOT complex, the major eukaryotic deadenylase. While CPEB4 is primarily known for its ability to stimulate cytoplasmic polyadenylation, our findings establish an additional function for CPEB4 as an RBP that enhances the degradation of short-lived IEG mRNAs.
HostingRepository	PRIDE
AnnounceDate	2022-08-22
AnnouncementXML	Submission_2022-08-22_01:20:27.704.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Ruppert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-05 05:00:41	ID requested
⏵ 1	2022-08-22 01:20:28	announced

Dataset with its publication pending

submitter keyword: RNA-binding proteins (RBPs), acetylation, HDAC inhibition, CPEB4, mRNA turnover

Thomas Ruppert
contact affiliation	Zentrum fuer Molekulare Biologie, University Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
contact email	t.ruppert@zmbh.uni-heidelberg.de
lab head
Thomas Ruppert
contact affiliation	ZMBH, Im Neuenheimer Feld 282, 69122 Heidelberg
contact email	t.ruppert@zmbh.uni-heidelberg.de
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/2022/08/PXD029592

PRIDE project URI

• PRIDE
  1. PXD029592
     1. Label: PRIDE project
     2. Name: Poly(A) RNA interactome capture upon HDAC inhibition by Romidepsin