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Nonstop mRNAs generate a ground state of mitochondrial gene expression noise

Lookup NU author(s): Dr Uwe RichterORCiD, Professor Robert Taylor

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

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.

Publication metadata

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

Year: 2022

Volume: 8

Issue: 46

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)

URL: https://doi.org/10.1126/sciadv.abq5234

DOI: 10.1126/sciadv.abq5234

PubMed id: 36399564

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