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- W2891942618 abstract "Abstract Post-transcriptional RNA modifications play a critical role in the pathogenesis of human mitochondrial disorders, but the mechanisms by which specific modifications affect mitochondrial protein synthesis remain poorly understood. Here we used a quantitative RNA sequencing approach to investigate, at nucleotide resolution, the stoichiometry and methyl modifications of the entire mitochondrial tRNA pool, and establish the relevance to human disease. We discovered that a N 1 -methyladenosine (m 1 A) modification is missing at position 58 in the mitochondrial tRNA Lys of patients with the mitochondrial DNA mutation m.8344 A > G associated with MERRF (myoclonus epilepsy, ragged-red fibers). By restoring the modification on the mitochondrial tRNA Lys , we demonstrated the importance of the m 1 A58 to translation elongation and the stability of selected nascent chains. Our data indicates regulation of post-transcriptional modifications on mitochondrial tRNAs is finely tuned for the control of mitochondrial gene expression. Collectively, our findings provide novel insight into the regulation of mitochondrial tRNAs and reveal greater complexity to the molecular pathogenesis of MERRF." @default.
- W2891942618 created "2018-09-27" @default.
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- W2891942618 date "2018-09-27" @default.
- W2891942618 modified "2023-10-17" @default.
- W2891942618 title "RNA modification landscape of the human mitochondrial tRNALys regulates protein synthesis" @default.
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- W2891942618 doi "https://doi.org/10.1038/s41467-018-06471-z" @default.
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