ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR254/028/SRR25487128/SRR25487128.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR254/029/SRR25487129/SRR25487129.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR254/030/SRR25487130/SRR25487130.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR254/032/SRR25487132/SRR25487132.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR254/031/SRR25487131/SRR25487131.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR254/033/SRR25487133/SRR25487133.fastq.gzprimaryOK200GenomicsFundamental Neurosciences, University of Lausannehttps://www.ebi.ac.uk/ena/browser/view/PRJNA1000965Mus musculusxref:PubMed:38704026In this study, we discovered cytosolic and mitochondrial fragments resulting from tRNA and mt-tRNA cleavage, which may act as new regulators of cellular and metabolic functions. We analyzed hundreds of these fragments in the pancreatic islets of db/db mice and compared them to heterozygous control db/+ mice. At 16 weeks of age, db/db mice exhibit obesity, insulin resistance, and glucose intolerance. In our analysis, we identified 3858 tRFs in the islets of db/db mice, among which 342 exhibited significant changes (≥ 2 fold adjusted p value ≤ 0.05) compared to controls. Of these, 199 tRFs showed increased levels, while 170 tRFs showed decreased levels in the pre-diabetic mice. Notably, a striking majority (147 out of 170) of the tRFs with reduced abundance in the islets of db/db mice were derived from the cleavage of tRNAs encoded by the mitochondrial genome. Our findings reveal a significant reshaping of mitochondrial tRFs in pre-diabetic conditions, coinciding with a well-established mitochondrial metabolic defect under these conditions. Specifically, we demonstrated that a fragment (named mt-tRF-LeuTAA) resulting from the cleavage of mt-tRNA-LeuTAA, encoded by the mitochondrial genome and found to be reduced in the islets of db/db mice, acts as a key regulator of mitochondrial OXPHOS functions, mitochondrial membrane potential, the insulin secretory capacity of ß-cells, and the insulin sensitivity of myotube muscle cells. Overall design: In order to characterize the expression profile of tRFs (tRNA-derived fragments) in a pre-diabetic context, we isolated total RNA from pancreatic islets of three db/db mice and compared it to that of three heterozygous controls (db/+ mice).ENAfalseStudy of the tRNA-derived fragment expression profile in mouse pancreatic islets of pre-diabetic obese db/db miceStudy of the tRNA-derived fragment expression profile in mouse pancreatic islets of pre-diabetic obese db/db mice2025-09-242024-06-23PRJNA1000965GSE2397861009038704026