The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure

Abstract

tRNAs are crucial noncoding RNA molecules that serve as amino acid carriers during protein synthesis. The transcription of tRNA genes is a highly regulated process. The tRNA pool is tissue and cell specific, it varies during development, and it is modulated by the environment. tRNAs are highly posttranscriptionally modified by specific tRNA-modifying enzymes. The tRNA modification signature of a cell determines the tRNA epitranscriptome. Perturbations in the tRNA epitranscriptome, as a consequence of mutations in tRNAs and tRNA-modifying enzymes or environmental exposure, have been associated with human disease, including diabetes. tRNA fragmentation induced by impaired tRNA modifications or dietary factors has been linked to pancreatic β-cell demise and paternal inheritance of metabolic traits. Herein, we review recent findings that associate tRNA epitranscriptome perturbations with diabetes.