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Lookup NU author(s): Dr Uwe RichterORCiD,
Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
A stop codon within the mRNA facilitates coordinated termination of protein synthesis, releasing the nascent polypeptide from the ribosome. This essential step in gene expression is impeded with transcripts lacking a stop codon, generating nonstop ribosome complexes. Here, we use deep sequencing to investigate sources of nonstop mRNAs generated from the human mitochondrial genome. We identify diverse types of nonstop mRNAs on mitochondrial ribosomes that are resistant to translation termination by canonical release factors. Failure to resolve these aberrations by the mitochondrial release factor in rescue (MTRFR) imparts a negative regulatory effect on protein synthesis that is associated with human disease. Our findings reveal a source of underlying noise in mitochondrial gene expression and the importance of responsive ribosome quality control mechanisms for cell fitness and human health.
Author(s): Ng KY, Lutfullahoglu Bal G, Richter U, Safronov O, Paulin L, Dunn CD, Paavilainen VO, Richer J, Newman WG, Taylor RW, Battersby BJ
Publication type: Article
Publication status: Published
Journal: Science Advances
Online publication date: 18/11/2022
Acceptance date: 22/10/2022
Date deposited: 08/12/2022
ISSN (electronic): 2375-2548
Publisher: American Association for the Advancement of Science (AAAS)
PubMed id: 36399564
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