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ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy

Lookup NU author(s): Dr Joanna Rorbach, Professor Robert Taylor


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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.

Publication metadata

Author(s): Haack 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

Publication type: Article

Publication status: Published

Journal: American Journal of Human Genetics

Year: 2013

Volume: 93

Issue: 2

Pages: 211-223

Print publication date: 01/08/2013

ISSN (print): 0002-9297

ISSN (electronic):

Publisher: Cell Press


DOI: 10.1016/j.ajhg.2013.06.006


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Funder referenceFunder name
UK Medical Research Council
01GM1207E-Rare project GENOMIT
096919/Z/11/ZWellcome Trust
FWF I 920-B13E-Rare project GENOMIT
GGP11011Fondazione Telethon
mitoNET 01GM1113CGerman Network for mitochondrial disorders (mitoNET)
SysMBo 0315494AGerman Bundesministerium fur Bildung und Forschung (BMBF)