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

Autor: Xavier V; The CRUK Scotland Institute, Glasgow, UK.; Department of Molecular and Cellular Biology, University of Geneva, Genève, Switzerland., Martinelli S; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Corbyn R; The CRUK Scotland Institute, Glasgow, UK., Pennie R; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Rakovic K; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Powley IR; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Officer-Jones L; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Ruscica V; https://ror.org/00vtgdb53 MRC-University of Glasgow Centre for Virus Research, Glasgow, UK., Galloway A; The CRUK Scotland Institute, Glasgow, UK., Carlin LM; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Cowling VH; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Le Quesne J; The CRUK Scotland Institute, Glasgow, UK.; https://ror.org/00vtgdb53 School of Cancer Sciences, University of Glasgow, Glasgow, UK., Martinou JC; Department of Molecular and Cellular Biology, University of Geneva, Genève, Switzerland Jean-Claude.Martinou@unige.ch., 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.
Jazyk: angličtina
Zdroj: Life science alliance [Life Sci Alliance] 2024 Aug 29; Vol. 7 (11). Date of Electronic Publication: 2024 Aug 29 (Print Publication: 2024).
DOI: 10.26508/lsa.202402764
Abstrakt: 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.
(© 2024 Xavier et al.)
Databáze: MEDLINE