RNA modification landscape of the human mitochondrial tRNA(LYs) regulates protein synthesis

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http://hdl.handle.net/10138/289804

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Richter , U , Evans , M E , Clark , W C , Marttinen , P , Shoubridge , E A , Suomalainen , A , Wredenberg , A , Wedell , A , Pan , T & Battersby , B J 2018 , ' RNA modification landscape of the human mitochondrial tRNA(LYs) regulates protein synthesis ' , Nature Communications , vol. 9 , 3966 . https://doi.org/10.1038/s41467-018-06471-z

Title: RNA modification landscape of the human mitochondrial tRNA(LYs) regulates protein synthesis
Author: Richter, Uwe; Evans, Molly E.; Clark, Wesley C.; Marttinen, Paula; Shoubridge, Eric A.; Suomalainen, Anu; Wredenberg, Anna; Wedell, Anna; Pan, Tao; Battersby, Brendan J.
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Research Programs Unit
University of Helsinki, Institute of Biotechnology
Date: 2018-09-27
Language: eng
Number of pages: 11
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/289804
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.
Subject: WOBBLE MODIFICATION DEFICIENCY
MYOCLONIC EPILEPSY
BASE-RESOLUTION
MESSENGER-RNA
MUTATION
TRANSLATION
DISEASE
DEFECT
MERRF
EXPRESSION
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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