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Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly

Lookup NU author(s): Dr Jim StewartORCiD

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Abstract

The regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. We generated conditional knockout mice of the endoribonuclease component of the RNase P complex, MRPP3, and report that it is essential for life and that heart and skeletal-muscle-specific knockout leads to severe cardiomyopathy, indicating that its activity is non-redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq enabled us to identify that in vivo 5' tRNA cleavage precedes 3' tRNA processing, and this is required for the correct biogenesis of the mitochondrial ribosomal subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA containing the 16S rRNA. Taken together, our data show that RNA processing links transcription to translation via assembly of the mitoribosome.

Publication metadata

Author(s): Rackham O, Busch JD, Matic S, Siira SJ, Kuznetsova I, Atanassov I, Ermer JA, Shearwood AMJ, Richman TR, Stewart JB, Mourier A, Milenkovic D, Larsson NG, Filipovska A

Publication type: Article

Publication status: Published

Journal: Cell Reports

Year: 2016

Volume: 16

Issue: 7

Pages: 1874-1890

Print publication date: 16/08/2016

Online publication date: 04/08/2016

Acceptance date: 13/07/2016

Date deposited: 12/11/2020

ISSN (print): 2211-1247

Publisher: Cell Press

URL: https://doi.org/10.1016/j.celrep.2016.07.031

DOI: 10.1016/j.celrep.2016.07.031

PubMed id: 27498866

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