PXD034343 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | eIF4A1 unwinding activity is RNA sequence-specifically deployed through eIF4A1-multimerisation to facilitate translation of mRNAs with local repressive RNA structure |
Description | Oncogenic translational programmes are an emerging hallmark of cancer and often driven by dysregulation of signaling pathways including KRAS and mTORC that converge on the eukaryotic translation initiation (eIF) 4F complex. Altered eIF4F activity promotes translation of oncogene mRNAs that typically contain highly structured 5’UTRs rendering their translation strongly dependent on RNA unwinding by DEAD-box helicase eIF4A1 subunit of the eIF4F complex. In addition, eIF4A1 separately functions to load mRNA into the 43S pre-initiation complex (PIC), an essential step for the translation of cellular mRNA. While eIF4A1-dependent mRNAs have been widely investigated, it is still unclear if highly structured mRNAs recruit and activate eIF4A1 unwinding specifically. Here, we uncover that unwinding by eIF4A1 is activated in an RNA sequence-dependent manner in cells. Our data demonstrate that eIF4A1-dependent mRNAs contain specific RNA sequences, particularly enriched for polypurine-motifs, in their 5’UTR which recruit and specifically stimulate unwinding of local repressive RNA structure by eIF4A1 in an RNA sequence-dependent manner to facilitate translation. Mechanistically, we show that polypurine-rich sequences trigger the formation of RNA sequence-specific multimeric eIF4A1-complexes, assembled of catalytically distinct eIF4A1 subunits, the joint activity of which enhances RNA unwinding activity. Together with our structural data, we describe a model in which conformational changes within eIF4A1 and the RNA through the process of eIF4A1 multimerisation, lead to an optimal interaction of eIF4A1-unwinding subunits with the structured RNA region which enhances unwinding. Hence, we conclude that RNA sequences in addition to protein cofactors contribute to the regulation of cellular eIF4A1 function and promotion of translation of eIF4A1-unwinding dependent mRNAs. |
HostingRepository | PRIDE |
AnnounceDate | 2023-01-17 |
AnnouncementXML | Submission_2023-01-17_06:09:58.976.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | KellyHodge |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-06-06 02:04:41 | ID requested | |
⏵ 1 | 2023-01-17 06:09:59 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: proteomics, TMT,eIF4A1, pulse SILAC |
Contact List
SaraZanivan |
contact affiliation | Head of Proteomics, Beatson Institute for Cancer Research |
contact email | Sara.Zanivan@glasgow.ac.uk |
lab head | |
KellyHodge |
contact affiliation | CRUK Beatson Institute |
contact email | k.hodge@beatson.gla.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034343
- Label: PRIDE project
- Name: eIF4A1 unwinding activity is RNA sequence-specifically deployed through eIF4A1-multimerisation to facilitate translation of mRNAs with local repressive RNA structure