ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.

TitleELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.
Publication TypeJournal Article
Year of Publication2013
AuthorsHaack, TB, Kopajtich, R, Freisinger, P, Wieland, T, Rorbach, J, Nicholls, TJ, Baruffini, E, Walther, A, Danhauser, K, Zimmermann, FA, Husain, RA, Schum, J, Mundy, H, Ferrero, I, Strom, TM, Meitinger, T, Taylor, RW, Minczuk, M, Mayr, JA, Prokisch, H
JournalAm J Hum Genet
Date Published2013 Aug 08
KeywordsAmino Acid Sequence, Cardiomyopathy, Hypertrophic, Cell Nucleus, Electron Transport, Endoribonucleases, Female, Fibroblasts, Genetic Complementation Test, Humans, Infant, Male, Mitochondria, Molecular Sequence Data, Muscles, Mutation, Neoplasm Proteins, Pedigree, RNA Processing, Post-Transcriptional, RNA, Messenger, RNA, Mitochondrial, RNA, Ribosomal, RNA, Transfer, Saccharomyces cerevisiae

The human mitochondrial genome encodes RNA components of its own translational machinery to produce the 13 mitochondrial-encoded subunits of the respiratory chain. Nuclear-encoded gene products are essential for all processes within the organelle, including RNA processing. Transcription of the mitochondrial genome generates large polycistronic transcripts punctuated by the 22 mitochondrial (mt) tRNAs that are conventionally cleaved by the RNase P-complex and the RNase Z activity of ELAC2 at 5' and 3' ends, respectively. We report the identification of mutations in ELAC2 in five individuals with infantile hypertrophic cardiomyopathy and complex I deficiency. We observed accumulated mtRNA precursors in affected individuals muscle and fibroblasts. Although mature mt-tRNA, mt-mRNA, and mt-rRNA levels were not decreased in fibroblasts, the processing defect was associated with impaired mitochondrial translation. Complementation experiments in mutant cell lines restored RNA processing and a yeast model provided additional evidence for the disease-causal role of defective ELAC2, thereby linking mtRNA processing to human disease.

Alternate JournalAm. J. Hum. Genet.
Citation Key10.1016/j.ajhg.2013.06.006
PubMed ID23849775
PubMed Central IDPMC3738821
Grant ListGGP11011 / / Telethon / Italy
096919/Z/11/Z / / Wellcome Trust / United Kingdom
MR/K000608/1 / / Medical Research Council / United Kingdom
096919 / / Wellcome Trust / United Kingdom
MC_U105697135 / / Medical Research Council / United Kingdom