ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.
Am J Hum Genet
; 93(2): 211-23, 2013 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-23849775
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Hipertrófica
/
RNA Mensageiro
/
Processamento Pós-Transcricional do RNA
/
Mitocôndrias
/
Mutação
/
Proteínas de Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article