Concerted regulation of mitochondrial and nuclear non-coding RNAs by a dual-targeted RNase Z.

Autor: Siira SJ; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Rossetti G; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Richman TR; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Perks K; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Ermer JA; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Kuznetsova I; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Hughes L; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Shearwood AJ; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia., Viola HM; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia., Hool LC; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.; School of Human Sciences (Physiology), The University of Western Australia, Crawley, WA, Australia., Rackham O; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia.; School of Molecular Sciences, The University of Western Australia, Nedlands, WA, Australia., Filipovska A; Harry Perkins Institute of Medical Research and Centre for Medical Research, Nedlands, WA, Australia aleksandra.filipovska@uwa.edu.au.; School of Molecular Sciences, The University of Western Australia, Nedlands, WA, Australia.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2018 Oct; Vol. 19 (10). Date of Electronic Publication: 2018 Aug 20.
DOI: 10.15252/embr.201846198
Abstrakt: The molecular roles of the dually targeted ElaC domain protein 2 (ELAC2) during nuclear and mitochondrial RNA processing in vivo have not been distinguished. We generated conditional knockout mice of ELAC2 to identify that it is essential for life and its activity is non-redundant. Heart and skeletal muscle-specific loss of ELAC2 causes dilated cardiomyopathy and premature death at 4 weeks. Transcriptome-wide analyses of total RNAs, small RNAs, mitochondrial RNAs, and miRNAs identified the molecular targets of ELAC2 in vivo We show that ELAC2 is required for processing of tRNAs and for the balanced maintenance of C/D box snoRNAs, miRNAs, and a new class of tRNA fragments. We identify that correct biogenesis of regulatory non-coding RNAs is essential for both cytoplasmic and mitochondrial protein synthesis and the assembly of mitochondrial ribosomes and cytoplasmic polysomes. We show that nuclear tRNA processing is required for the balanced production of snoRNAs and miRNAs for gene expression and that 3' tRNA processing is an essential step in the production of all mature mitochondrial RNAs and the majority of nuclear tRNAs.
(© 2018 The Authors.)
Databáze: MEDLINE
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