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Mutations in the mitochondrial genome are associated with multiple diseases and biological processes; however, little is known about the extent of sequence variation in the mitochondrial transcriptome. By ultra-deeply sequencing mitochondrial RNA (>6000×) from the whole blood of ~1000 individuals from the CARTaGENE project, we identified remarkable levels of sequence variation within and across individuals, as well as sites that show consistent patterns of posttranscriptional modification. Using a genome-wide association study, we find that posttranscriptional modification of functionally important sites in mitochondrial transfer RNAs (tRNAs) is under strong genetic control, largely driven by a missense mutation in MRPP3 that explains ~22% of the variance. These results reveal a major nuclear genetic determinant of posttranscriptional modification in mitochondria and suggest that tRNA posttranscriptional modification may affect cellular energy production.

Original publication

DOI

10.1126/science.1251110

Type

Journal article

Journal

Science

Publication Date

25/04/2014

Volume

344

Pages

413 - 415

Keywords

Adult, Aged, Base Sequence, DNA, Mitochondrial, Female, Genetic Variation, Genome, Mitochondrial, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Male, Methylation, Middle Aged, Mutation, Missense, Polymorphism, Single Nucleotide, RNA, RNA Processing, Post-Transcriptional, RNA, Mitochondrial, RNA, Transfer, Ribonuclease P, Sequence Analysis, DNA, Sequence Analysis, RNA, Transcriptome