Maturation of selected human mitochondrial tRNAs requires deadenylation
- University of Cambridge, United Kingdom
Abstract
Human mitochondria contain a genome (mtDNA) that encodes essential subunits of the oxidative phosphorylation system. Expression of mtDNA entails multi-step maturation of precursor RNA. In other systems, the RNA life cycle involves surveillance mechanisms, however, the details of RNA quality control have not been extensively characterised in human mitochondria. Using a mitochondrial ribosome profiling and mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) assay we identify the poly(A)-specific exoribonuclease PDE12 as a major factor for the quality control of mitochondrial non-coding RNAs. The lack of PDE12 results in a spurious polyadenylation of the 3' ends of the mitochondrial (mt-) rRNA and mt-tRNA. While the aberrant adenylation of 16S mt-rRNA did not affect the integrity of the mitoribosome, spurious poly(A) additions to mt-tRNA led to reduced levels of aminoacylated pool of certain mt-tRNAs and mitoribosome stalling at the corresponding codons. Therefore, our data uncover a new, deadenylation-dependent mtRNA maturation pathway in human mitochondria.
Data availability
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Analysis of mitochondrial gene expression with Ribosome ProfilingPublicly available at ArrayExpress (accession no. E-MTAB-5519).
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Application of next generation sequencing approaches to assess effects of PDE12 knockout on the mitochondrial transcriptomePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE95351).
Article and author information
Author details
Funding
Medical Research Council (MC_U105697135)
- Sarah F Pearce
- Joanna Rorbach
- Lindsey Van Haute
- Aaron R D'Souza
- Pedro Rebelo-Guiomar
- Christopher A Powell
- Michal Minczuk
Wellcome (106207)
- Ian Brierley
- Andrew E Firth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Timothy W Nilsen, Case Western Reserve University, United States
Version history
- Received: April 7, 2017
- Accepted: July 21, 2017
- Accepted Manuscript published: July 26, 2017 (version 1)
- Version of Record published: August 4, 2017 (version 2)
Copyright
© 2017, Pearce et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Maturation of selected human mitochondrial tRNAs requires deadenylation
eLife 6:e27596.
https://doi.org/10.7554/eLife.27596
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