Transfer RNAs (tRNAs) are highly post-transcriptionally modified molecules essential for protein translation.
tRNA modifications are introduced by specific tRNA-modifying enzymes. Mutations in these enzymes are associated with human disease1. Loss-of-function mutations in TRMT10A, a tRNA methyltransferase, cause early onset diabetes and microcephaly2. TRMT10A deficiency leads to hypomethylation and fragmentation of selected cytosolic tRNAs, and 5’tRNAGln fragments mediate TRMT10A-deficiency-induced β-cell apoptosis3. Interestingly, proinflammatory cytokines impair TRMT10A expression, and β-cells from type 1 diabetes patients have reduced TRMT10A levels suggesting that TRMT10A deficiency may not only contribute to β-cell demise in a rare genetic form of diabetes but also in type 1 diabetes.