PXD079726

PXD079726 is an original dataset announced via ProteomeXchange.

Title	Unbiased screen of human transcriptome reveals an unexpected role of 3'UTRs in translation initiation
Description	Although most eukaryotic mRNAs require a 5'-cap for translation initiation, some can also be translated through a poorly studied cap-independent pathway. Here we developed a circRNA-based system and unbiasedly identified more than 10,000 sequences in the human transcriptome that contain Cap-independent Translation Initiators (CiTIs). Surprisingly, most of the identified CiTIs are located in 3'UTRs, which mainly promote translation initiation in mRNAs bearing highly structured 5'UTR. Mechanistically, CiTI recruits several translation initiation factors including eIF3 and DHX29, which in turn unwind 5'UTR structures and facilitate ribosome scanning. Functionally, we showed that the translation of HIF1A mRNA, an endogenous DHX29 target, is antagonistically regulated by its 5'UTR structure and a new 3'-CiTI in response to hypoxia. Consistently, deletion of 3'-CiTI suppresses cell growth in hypoxia and tumor progression in vivo. Collectively, our study uncovers a new regulatory mode for translation where the 3'UTR actively participate in the translation initiation. ESI-LC-MS was used to identify trans-acting factors recruited by the 3'-CiTIs, which promote translation. We performed RNA affinity purification using the MS2-fused RNAs containing three different 3'-CiTIs (derived from EIF4G2, EIF3I and MBTPS1) and controls (Empty-ctrl and EIF4B). The purified RNP complexes were analyzed with mass spectrometry to identify 63 candidate proteins enriched in all three CiTI pulldowns.
HostingRepository	MassIVE
AnnounceDate	2026-07-19
AnnouncementXML	Submission_2026-07-19_10:04:04.666.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Olexandr Dybkov
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-15 16:01:29	ID requested
⏵ 1	2026-07-19 10:04:05	announced

no publication

submitter keyword: translation initiation, Cap-independent Translation Initiators (CiTIs), circRNA, DHX29, eIF3, DatasetType:Proteomics

Zefeng Wang
contact affiliation	1. Bio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai; 2. Shanghai CirCode Biomedicine Co. Ltd.; 3. Department of Systems Biology, Innovative Center of RNA Medicine, School of Life Sciences, Southern University of Science and Technology, Shenzhen
contact email	wangzf@sustech.edu.cn
lab head
Prof. Henning Urlaub
contact affiliation	1. Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences; 2. Bioanalytics, University Medical Center Goettingen
contact email	henning.urlaub@mpinat.mpg.de
lab head
Olexandr Dybkov
contact affiliation	MPINAT
contact email	odybkov@mpinat.mpg.de
dataset submitter

MassIVE dataset URI

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://massive-ftp.ucsd.edu/v13/MSV000102164/