---
pmid: '27974379'
title: A pseudouridine synthase module is essential for mitochondrial protein synthesis
  and cell viability.
authors:
- Antonicka H
- Choquet K
- Lin ZY
- Gingras AC
- Kleinman CL
- Shoubridge EA
journal: EMBO Rep
year: '2017'
full_text_available: false
pmcid: PMC5210091
doi: 10.15252/embr.201643391
---

# A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability.
**Authors:** Antonicka H, Choquet K, Lin ZY, Gingras AC, Kleinman CL, Shoubridge EA
**Journal:** EMBO Rep (2017)
**DOI:** [10.15252/embr.201643391](https://doi.org/10.15252/embr.201643391)
**PMC:** [PMC5210091](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210091/)

## Abstract

1. EMBO Rep. 2017 Jan;18(1):28-38. doi: 10.15252/embr.201643391. Epub 2016 Dec
14.

A pseudouridine synthase module is essential for mitochondrial protein synthesis 
and cell viability.

Antonicka H(1), Choquet K(1), Lin ZY(2), Gingras AC(2)(3), Kleinman CL(4), 
Shoubridge EA(5).

Author information:
(1)Department of Human Genetics, Montreal Neurological Institute, McGill 
University, Montreal, QC, Canada.
(2)Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, 
Canada.
(3)Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
(4)Department of Human Genetics, Segal Cancer Centre and Lady Davis Institute, 
Jewish General Hospital, McGill University, Montréal, QC, Canada.
(5)Department of Human Genetics, Montreal Neurological Institute, McGill 
University, Montreal, QC, Canada eric@ericpc.mni.mcgill.ca.

Pseudouridylation is a common post-transcriptional modification in RNA, but its 
functional consequences at the cellular level remain largely unknown. Using a 
proximity-biotinylation assay, we identified a protein module in mitochondrial 
RNA granules, platforms for post-transcriptional RNA modification and ribosome 
assembly, containing several proteins of unknown function including three 
uncharacterized pseudouridine synthases, TRUB2, RPUSD3, and RPUSD4. TRUB2 and 
RPUSD4 were previously identified as core essential genes in CRISPR/Cas9 
screens. Depletion of the individual enzymes produced specific mitochondrial 
protein synthesis and oxidative phosphorylation assembly defects without 
affecting mitochondrial mRNA levels. Investigation of the molecular targets in 
mitochondrial RNA by pseudouridine-Seq showed that RPUSD4 plays a role in the 
pseudouridylation of a single residue in the 16S rRNA, a modification that is 
essential for its stability and assembly into the mitochondrial ribosome, while 
TRUB2/RPUSD3 were similarly involved in pseudouridylating specific residues in 
mitochondrial mRNAs. These results establish essential roles for 
epitranscriptomic modification of mitochondrial RNA in mitochondrial protein 
synthesis, oxidative phosphorylation, and cell survival.

© 2016 The Authors.

DOI: 10.15252/embr.201643391
PMCID: PMC5210091
PMID: 27974379 [Indexed for MEDLINE]