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

ABSTRACT: 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 nuclear and mitochondrial molecular targets of ELAC2 in vivo. We show that ELAC2 is required for processing of nuclear and mitochondrial tRNAs and for the balanced maintenance of C/D box snoRNAs, a new class of tRNA fragments, and miRNAs. We identify that correct biogenesis of regulatory non-coding RNAs is essential for both cytoplasmic and mitochondrial protein synthesis as well as the assembly of mitochondrial ribosomes and cytoplasmic polysomes. Taken together our data show that nuclear tRNA processing is required for the balanced production of snoRNAs and miRNAs for gene expression and that 3′ tRNA processing follows 5′ tRNA processing but nevertheless is an essential step in the production of all mature mitochondrial RNAs and the majority of nuclear tRNAs.

ORGANISM(S): Mus musculus

PROVIDER: GSE111225 | GEO | 2018/08/20

REPOSITORIES: GEO

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