PXD014764

PXD014764 is an original dataset announced via ProteomeXchange.

Title	eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5’UTR.
Description	Regulation of the mRNA life-cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. Here we show eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar properties to chemically inhibited eIF4A1. We demonstrate that eIF4A2 exerts it repressive effect by binding purine-rich motifs which are enriched in the 5’UTR directly upstream of the AUG start codon. The data supports a model whereby purine motifs towards the 3’ end of the 5’UTR are associated with increased ribosome occupancy and possible uORF activation similar to that observed for mRNAs affected by inhibited eIF4A1.
HostingRepository	PRIDE
AnnounceDate	2019-10-08
AnnouncementXML	Submission_2019-10-08_07:51:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelly Hodge
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	isotope labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-25 04:32:19	ID requested
⏵ 1	2019-10-08 07:51:27	announced

Dataset with its publication pending

submitter keyword: DEAD-Box Helicase, Translation control, pulsed SILAC

Sara Rossana Zanivan
contact affiliation	CRUK Beatson Institute, Switchback Road, Glasgow G61 1BD, UK
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Kelly Hodge
contact affiliation	CRUK Beatson Institute
contact email	k.hodge@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014764
     1. Label: PRIDE project
     2. Name: eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5’UTR.