Study of the tRNA-derived fragment expression profile in mouse pancreatic islets of pre-diabetic obese db/db mice

ABSTRACT: In 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE239786 | GEO | 2024/05/14

REPOSITORIES: GEO