Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction

ABSTRACT: In this study, we discovered cytosolic and mitochondrial small non-coding RNAs (tRNA-derived fragments, piRNAs and microRNAs) which may act as new regulators of cellular and metabolic functions. We analzyed the expression profile and function of tRNA-derived fragments in a previous study (https://doi.org/10.1016/j.molmet.2024.101955). In this current study, we focused our analysis on hundreds of microRNAs and piRNAs in the mitochondrial fractions versus whole cell lysates from pancreatic islets of progeny of rats exposed to a low-protein (LP) diet during in utero and lactation period and compared them to control rats. At 22 days of age, LP-exposed rats exhibit a reduced body weight and a decreased beta-cell mass. These animals are more prone to develop diabetes and display a glucose intolerance at adulthood. In our analysis, we identified 6164 tRFs, 543 microRNAs, 118 piRNAs and 32 other types of small non-coding RNAs in the islets of LP-exposed rats, among which 400 exhibited significant changes (total read counts ≥ 13 cutoff, p ≤ 0.05) compared to controls. Of these, 167 tRFs showed increased levels, while 233 small non-coding RNAs showed decreased levels in the LP-exposed rat islets. Analysis of mictochondrial content revealed the presence of 548 tRNA-derived fragments, 33 microRNAs, 18 piRNAs and 22 other types of small non-coding RNAs in the mitochondrial fractions of control rat islets while the mitochondrial fractions of LP-exposed rat islets contained 564 tRNA-derived fragments, 23 microRNAs, 9 piRNAs and 23 other types of small non-coding RNAs. Our analysis revaled 10 microRNAs that are concomitantly enriched in the mitochondria while being reduced in cytosol of LP-exposed islet cells. Our findings reveal a significant reshaping of mitochondrial small non-coding RNAs in pre-diabetic conditions, coinciding with a well-established mitochondrial metabolic defect under these conditions.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE303428 | GEO | 2026/01/02

REPOSITORIES: GEO