Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression.


Journal

Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869

Informations de publication

Date de publication:
Nov 2024
Historique:
received: 10 04 2024
revised: 19 08 2024
accepted: 21 08 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 29 8 2024
Statut: epublish

Résumé

Mitochondrial gene expression is a compartmentalised process essential for metabolic function. The replication and transcription of mitochondrial DNA (mtDNA) take place at nucleoids, whereas the subsequent processing and maturation of mitochondrial RNA (mtRNA) and mitoribosome assembly are localised to mitochondrial RNA granules. The bidirectional transcription of circular mtDNA can lead to the hybridisation of polycistronic transcripts and the formation of immunogenic mitochondrial double-stranded RNA (mt-dsRNA). However, the mechanisms that regulate mt-dsRNA localisation and homeostasis are largely unknown. With super-resolution microscopy, we show that mt-dsRNA overlaps with the RNA core and associated proteins of mitochondrial RNA granules but not nucleoids. Mt-dsRNA foci accumulate upon the stimulation of cell proliferation and their abundance depends on mitochondrial ribonucleotide supply by the nucleoside diphosphate kinase, NME6. Consequently, mt-dsRNA foci are profuse in cultured cancer cells and malignant cells of human tumour biopsies. Our results establish a new link between cell proliferation and mitochondrial nucleic acid homeostasis.

Identifiants

pubmed: 39209534
pii: 7/11/e202402764
doi: 10.26508/lsa.202402764
pmc: PMC11361371
pii:
doi:

Substances chimiques

RNA, Mitochondrial 0
RNA, Double-Stranded 0
DNA, Mitochondrial 0
Nucleoside-Diphosphate Kinase EC 2.7.4.6

Banques de données

PDB
['2R20']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024 Xavier et al.

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Auteurs

Vanessa Xavier (V)

The CRUK Scotland Institute, Glasgow, UK.
Department of Molecular and Cellular Biology, University of Geneva, Genève, Switzerland.

Silvia Martinelli (S)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Ryan Corbyn (R)

The CRUK Scotland Institute, Glasgow, UK.

Rachel Pennie (R)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Kai Rakovic (K)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Ian R Powley (IR)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Leah Officer-Jones (L)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Vincenzo Ruscica (V)

https://ror.org/00vtgdb53 MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

Alison Galloway (A)

The CRUK Scotland Institute, Glasgow, UK.

Leo M Carlin (LM)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Victoria H Cowling (VH)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

John Le Quesne (J)

The CRUK Scotland Institute, Glasgow, UK.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

Jean-Claude Martinou (JC)

Department of Molecular and Cellular Biology, University of Geneva, Genève, Switzerland Jean-Claude.Martinou@unige.ch.

Thomas MacVicar (T)

The CRUK Scotland Institute, Glasgow, UK Thomas.MacVicar@glasgow.ac.uk.
https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK.

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Classifications MeSH