PXD073007-1

PXD073007 is an original dataset announced via ProteomeXchange.

Title	5′ UTR length regulates the production of alternative N-terminal protein isoforms in health and disease
Description	The 5′ untranslated region (5′ UTR) of an mRNA is classically viewed as a regulatory region that controls the amount of protein production, but not the resulting protein sequence. Here, we demonstrate that 5′ UTR length also plays a direct role in alternative N-terminal protein isoform production by controlling start codon selection. We find that very short 5′ UTRs enhance leaky scanning, thereby promoting the production of truncated alternative N-terminal protein isoforms. Changes in 5′ UTR length due to alternative transcription initiation can tune the relative abundance of alternative N-terminal isoforms from the same gene. In addition, we identify mutations in rare genetic diseases that alter 5′ UTR length, including a deletion in the VHL 5′ UTR in von Hippel–Lindau disease that shifts translation toward the shorter VHLp19 isoform. Together, our results implicate 5′ UTR length as a determinant of alternative N-terminal isoform production and reveal an underappreciated mechanism by which noncoding mutations can reshape the proteome.
HostingRepository	PRIDE
AnnounceDate	2026-03-13
AnnouncementXML	Submission_2026-03-13_05:52:21.348.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD073007
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jimmy Ly
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-13 06:43:18	ID requested
⏵ 1	2026-03-13 05:52:22	announced

Ly J, Smith EM, Di Bernardo M, Tao YF, Black EM, Khalizeva E, Cheeseman IM, 5' UTR length regulates alternative N-terminal protein isoform production in health and disease. bioRxiv, ():(2026) [pubmed]

10.64898/2026.01.20.700518;

10.6019/PXD073007;

submitter keyword: CFD, translation initiation, Alternative N-terminal isoform

Iain Cheeseman
contact affiliation	Whitehead Institute and MIT
contact email	icheese@wi.mit.edu
lab head
Jimmy Ly
contact affiliation	PhD student
contact email	jimmyly@wi.mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073007
     1. Label: PRIDE project
     2. Name: 5′ UTR length regulates the production of alternative N-terminal protein isoforms in health and disease