PXD065746-1

PXD065746 is an original dataset announced via ProteomeXchange.

Title	5’tRNA-derived fragments modulate beta cell homeostasis and islet macrophage activation in type 2 diabetes – Mouse islets proteomics
Description	During obesity and type 2 diabetes, pancreatic β-cells face chronic environmental stress, while islet-resident macrophages (iMACs) undergo metabolic reprogramming that exacerbates β-cell dysfunction. Stress-induced cleavage of tRNAs generates tRNA-derived fragments (tRFs), whose role in this context is not fully understood. We identify elevated levels of 5’tRFGlu(CTC) and 5’tRFGly(GCC) in β-cells and iMACs from db/db mice and in islets from type 2 diabetic (T2D) patients. Notably, 5’tRFGlu(CTC) is also induced under prediabetic conditions and inversely correlates with insulin secretion. Lipotoxic stress triggers their production via Angiogenin-mediated cleavage. Blocking 5’tRFGlu(CTC) in islets protects against β-cell apoptosis and restores insulin secretion under palmitate stress. Using a β-cell/macrophage co-culture system, we show that β-cell contact shapes a unique macrophage phenotype (iMAC-like) that shifts upon palmitate exposure—recapitulating in vivo observations. Inhibiting 5’tRFGlu(CTC) in iMAC-like cells prevents this activation switch, reduces β-cell stress, and improves insulin secretion. Mechanistically, 5’tRFGlu(CTC) interacts with RNA-binding proteins to regulate transcriptional and post-transcriptional pathways linked to immune activation, ECM remodeling, neurogenesis, and oxidative stress. Our study identifies 5’tRFs as key mediators of islet microenvironment remodeling in diabetes, offering new insights into intercellular stress signaling in metabolic disease.
HostingRepository	PRIDE
AnnounceDate	2026-03-12
AnnouncementXML	Submission_2026-03-12_03:46:15.660.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cristina Cosentino
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-03 08:37:04	ID requested
⏵ 1	2026-03-12 03:46:16	announced

Dataset with its publication pending

submitter keyword: tRNA, macrophages, non-coding RNAs, diabetes

Romano Regazzi
contact affiliation	Department of Fundamental Neurosciences, Rue du Bugnon 9, 1005, Lausanne
contact email	romano.regazzi@unil.ch
lab head
Cristina Cosentino
contact affiliation	University of Lausanne
contact email	cristina.cosentino@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065746
     1. Label: PRIDE project
     2. Name: 5’tRNA-derived fragments modulate beta cell homeostasis and islet macrophage activation in type 2 diabetes – Mouse islets proteomics