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Concerted regulation of mitochondrial and nuclear non‐coding RNA s by a dual‐targeted RN ase Z
Author(s) -
Siira Stefan J,
Rossetti Giulia,
Richman Tara R,
Perks Kara,
Ermer Judith A,
Kuznetsova Irina,
Hughes Laetitia,
Shearwood AnneMarie J,
Viola Helena M,
Hool Livia C,
Rackham Oliver,
Filipovska Aleksandra
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846198
Subject(s) - biology , small nucleolar rna , microbiology and biotechnology , rna , mitochondrial biogenesis , rna splicing , genetics , transcriptome , non coding rna , mitochondrion , gene expression , gene
The molecular roles of the dually targeted ElaC domain protein 2 ( ELAC 2) during nuclear and mitochondrial RNA processing in vivo have not been distinguished. We generated conditional knockout mice of ELAC 2 to identify that it is essential for life and its activity is non‐redundant. Heart and skeletal muscle‐specific loss of ELAC 2 causes dilated cardiomyopathy and premature death at 4 weeks. Transcriptome‐wide analyses of total RNA s, small RNA s, mitochondrial RNA s, and mi RNA s identified the molecular targets of ELAC 2 in vivo . We show that ELAC 2 is required for processing of tRNA s and for the balanced maintenance of C/D box sno RNA s, mi RNA s, and a new class of tRNA fragments. We identify that correct biogenesis of regulatory non‐coding RNA s 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 sno RNA s and mi RNA s for gene expression and that 3′ tRNA processing is an essential step in the production of all mature mitochondrial RNA s and the majority of nuclear tRNA s.