Science 25 April 2014:
Vol. 344 no. 6182 pp. 413-415
DOI: 10.1126/science.1251110
REPORT
High-Resolution Genomic Analysis of Human Mitochondrial RNA Sequence Variation
Alan Hodgkinson1,*, Youssef Idaghdour1,2,*,†, Elias Gbeha1, Jean-Christophe Grenier1, Elodie Hip-Ki1, Vanessa Bruat1, Jean-Philippe Goulet2, Thibault de Malliard1,2, Philip Awadalla1,2,‡
+ Author Affiliations
1CHU Sainte-Justine Research Centre, Department of Pediatrics, Faculty of Medicine, Université de Montreal, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada.
2CARTaGENE, 3333 Queen Mary Road, Office 493, Montreal, Quebec H3V 1A2, Canada.
+ Author Notes
?† Present address: Department of Biology, Division of Science and Mathematics, New York University Abu Dhabi, Post Office Box 129188, Abu Dhabi, United Arab Emirates.
?‡Corresponding author. E-mail: philip.awadalla@umontreal.ca
?* These authors contributed equally to this work.
ABSTRACTEDITOR'S SUMMARY
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.