Post-transcriptional methylation of mitochondrial-tRNA differentially contributes to mitochondrial pathology.

ABSTRACT: Human mitochondrial tRNAs (mt-tRNAs), critical for mitochondrial biogenesis, are frequently associated with pathogenic mutations. These mt-tRNAs have unusual sequence motifs and require post-transcriptional modifications to stabilize their fragile structures. However, whether a modification that stabilizes a wild-type (WT) mt-tRNA would also stabilize its pathogenic variants is unknown. Here we show that the N¹-methylation of guanosine at position 9 (m¹G9) of mt-Leu(UAA), while stabilizing the WT tRNA, has a destabilizing effect on variants associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). This differential effect is further demonstrated, as removal of the m¹G9 methylation, while damaging to the WT tR

SUBMITTER: Maharjan S 

PROVIDER: S-EPMC11489592 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature