Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Abstract

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.

People
Xavier, Vanessa
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Martinelli, Silvia
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Corbyn, Ryan
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441

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Pennie, Rachel
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Rakovic, Kai
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Powley, Ian R.
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Officer-Jones, Leah
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Ruscica, Vincenzo
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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Galloway, Alison
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Knop, Katarzyna and Gomez-Moreira, Carolina and Galloway, Alison and Ditsova, Dimitrinka and Cowling, Victoria H. (2024) RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression. Discovery Immunology, 3 (1): kyad021. ISSN 2754-2483

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Carlin, Leo M.
Author

Li, Chenxi and Liu, Qiongliang and Han, Lianyong and Zhang, Haiyun and Immler, Roland and Rathkolb, Birgit and Secklehner, Judith and de Angelis, Martin Hrabe and Yildirim, Ali Önder and Zeuschner, Dagmar and Nicke, Annette and Carlin, Leo M. and Sperandio, Markus and Stoeger, Tobias and Rehberg, Markus (2024) The eATP/P2×7R Axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. Advanced Science, 11 (45): 2404661. ISSN 2198-3844

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Santi, Alice and Kay, Emily J. and Neilson, Lisa J. and McGarry, Lynn and Lilla, Sergio and Mullin, Margaret and Paul, Nikki R. and Fercoq, Frederic and Koulouras, Grigorios and Rodriguez Blanco, Giovanny and Athineos, Dimitris and Mason, Susan and Hughes, Mark and Thomson, Gemma and Kieffer, Yann and Nixon, Colin and Blyth, Karen and Mechta-Grigoriou, Fatima and Carlin, Leo M. and Zanivan, Sara (2024) Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Science Signaling, 17 (827): eade0580. ISSN 1945-0877

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Cowling, Victoria H.
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Lukoszek, Radoslaw and Inesta-Vaquera, Francisco and Brett, Natasha J.M. and Liang, Shang and Hepburn, Lydia A. and Hughes, David J. and Pirillo, Chiara and Roberts, Edward W. and Cowling, Victoria H. (2024) CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection. Cell Reports, 43 (7): 114405. ISSN 2639-1856

Knop, Katarzyna and Gomez-Moreira, Carolina and Galloway, Alison and Ditsova, Dimitrinka and Cowling, Victoria H. (2024) RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression. Discovery Immunology, 3 (1): kyad021. ISSN 2754-2483

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Le Quesne, John
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

Frankell, Alexander M. and Dietzen, Michelle and Al Bakir, Maise and Lim, Emilia L. and Karasaki, Takahiro and Ward, Sophia and Veeriah, Selvaraju and Colliver, Emma and Huebner, Ariana and Bunkum, Abigail and Hill, Mark S. and Grigoriadis, Kristiana and Moore, David A. and Black, James R. M. and Liu, Wing Kin and Thol, Kerstin and Pich, Oriol and Watkins, Thomas B. K. and Naceur-Lombardelli, Cristina and Cook, Daniel E. and Salgado, Roberto and Wilson, Gareth A. and Bailey, Chris and Angelova, Mihaela and Bentham, Robert and Martínez-Ruiz, Carlos and Abbosh, Christopher and Nicholson, Andrew G. and Le Quesne, John and Biswas, Dhruva and Rosenthal, Rachel and Puttick, Clare and Hessey, Sonya and Lee, Claudia and Prymas, Paulina and Toncheva, Antonia and Smith, Jon and Xing, Wei and Nicod, Jerome and Price, Gillian and Kerr, Keith M. and Naidu, Babu and Middleton, Gary and Blyth, Kevin G. and Fennell, Dean A. and Forster, Martin D. and Lee, Siow Ming and Falzon, Mary and Hewish, Madeleine and Shackcloth, Michael J. and Lim, Eric and Benafif, Sarah and Russell, Peter and Boleti, Ekaterini and Krebs, Matthew G. and Lester, Jason F. and Papadatos-Pastos, Dionysis and Ahmad, Tanya and Thakrar, Ricky M. and Lawrence, David and Navani, Neal and Janes, Sam M. and Dive, Caroline and Blackhall, Fiona H. and Summers, Yvonne and Cave, Judith and Marafioti, Teresa and Herrero, Javier and Quezada, Sergio A. and Peggs, Karl S. and Schwarz, Roland F. and Van Loo, Peter and Miedema, Daniël M. and Birkbak, Nicolai J. and Hiley, Crispin T. and Hackshaw, Allan and Zaccaria, Simone and TRACERx Consortium and Jamal-Hanjani, Mariam and McGranahan, Nicholas and Swanton, Charles (2024) Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature, 631 (8022): E15. ISSN 1476-4687

Quiros, Adalberto Claudio and Coudray, Nicolas and Yeaton, Anna and Yang, Xinyu and Liu, Bojing and Le, Hortense and Chiriboga, Luis and Karimkhan, Afreen and Narula, Navneet and Moore, David A. and Park, Christopher Y. and Pass, Harvey and Moreira, Andre L. and Le Quesne, John and Tsirigos, Aristotelis and Yuan, Ke (2024) Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides. Nature Communications, 15: 4596. ISSN 2041-1723

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Martinou, Jean-Claude
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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MacVicar, Thomas
Author

Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077

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