ArticleNature communications2021
POLRMT mutations impair mitochondrial transcription causing neurological disease.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Mitochondrial DNA homeostasis: A novel therapeutic target for neurodegenerative diseases.Neural regeneration research · 2026Article
- Pathogenic POLRMT variants in mice impair mtDNA transcription and affect perinatal survival.JCI insight · 2026Article
- Targeting POLRMT-driven epigenetic remodeling of Wnt/β-catenin to eradicate colorectal cancer stem cell proliferation.Cell death and differentiation · 2026Article
- Longitudinal Blood DNA Methylation Changes During Weight-Loss Intervention and Dementia Progression Risk.Research square · 2026Article
- Maternal antenatal depression and offspring DNA methylation.Journal of affective disorders · 2026Article
- Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Expanding the Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease.Clinical genetics · 2026Article
- POLRMT overexpression increases mtDNA transcription without affecting steady-state mRNA levels.Life science alliance · 2025Article
- Identification of alternative splicing events in cows with A1A1 and A2A2 β-casein genotypes using large gap read mapping.BMC genomics · 2025Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Nucleic Acid Sequence Determinants of Transcriptional Pausing by the Human Mitochondrial RNA Polymerase (POLRMT).Biochemistry · 2025Article
- Human mitochondrial RNA polymerase structures reveal transcription start site and slippage mechanism.Molecular cell · 2025Article
- Structural basis for promoter recognition and transcription factor binding and release in human mitochondria.Molecular cell · 2025Article
- Mitochondrial Quality Control in Health and Disease.MedComm · 2025Review
- DragonRNA: Generality of DNA-primed RNA-extension activities by DNA-directed RNA polymerases.Nucleic acids research · 2025Article
- A prognostic model for laryngeal squamous cell carcinoma based on the mitochondrial metabolism-related genes.Translational cancer research · 2025Article
- Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila.iScience · 2025Article
- Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease.JCI insight · 2024Article
- Glycogen homeostasis and mtDNA expression require motor neuron to muscle TGFβ/Activin Signaling inbioRxiv : the preprint server for biology · 2024Article
- Article
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Authors and funding
39 authors at 14 institutions in 9 countries.
Monika Oláhová *Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Bradley Peter *Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Zsolt SzilagyiDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Hector Diaz-MaldonadoDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Meenakshi SinghDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Ewen W SommervilleWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Emma L BlakelyWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Jack J CollierWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Emily HobergDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Viktor StráneckýResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, 120 00, Czech Republic.
Hana HartmannováResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, 120 00, Czech Republic.
Anthony J BleyerResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, 120 00, Czech Republic.
Kim L McBrideCenter for Cardiovascular and Pulmonary Research, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, USA.ORCID 0000-0002-8407-8942
Sasigarn A BowdenDivision of Endocrinology, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, USA.ORCID 0000-0001-6917-5333
Zuzana KorandováResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, 120 00, Czech Republic.
Alena PecinováDepartment of Bioenergetics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.ORCID 0000-0002-0204-7502
Hans-Hilger RopersDepartment of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Kimia KahriziGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Hossein NajmabadiGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Mark A TarnopolskyDepartment of Pediatric and Medicines, Division of Neuromuscular and Neurometabolic Diseases, McMaster University Children's Hospital, Hamilton, Canada.
Lauren I BradyDepartment of Pediatric and Medicines, Division of Neuromuscular and Neurometabolic Diseases, McMaster University Children's Hospital, Hamilton, Canada.
K Nicole WeaverDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Carlos E PradaDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Katrin ÕunapDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.ORCID 0000-0002-4594-6364
Monica H WojcikBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Sander PajusaluDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.ORCID 0000-0002-5435-0781
Safoora B SyedaDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
Lynn PaisCenter for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Elicia A EstrellaDivision of Genetics & Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Christine C BruelsDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
Louis M KunkelDivision of Genetics & Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Peter B KangDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.ORCID 0000-0002-4270-7325
Penelope E BonnenDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Tomáš MráčekDepartment of Bioenergetics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Stanislav KmochResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, 120 00, Czech Republic.
Gráinne S GormanWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Maria FalkenbergDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0001-8713-173X
Claes M GustafssonDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden. claes.gustafsson@medkem.gu.se.ORCID 0000-0003-3531-8468
Robert W TaylorWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. robert.taylor@ncl.ac.uk.ORCID 0000-0002-7768-8873
University of Gothenburg · SEWellcome Centre for Mitochondrial Research · GBCharles University · CZBroad Institute · USCzech Academy of Sciences · CZUniversity of Florida · USBoston Children's Hospital · USCincinnati Children's Hospital Medical Center · USMcMaster Children's Hospital · CANationwide Children's Hospital · USUniversity of Social Welfare and Rehabilitation Sciences · IRBaylor College of Medicine · USJohannes Gutenberg University Mainz · DETartu University Hospital · EE
Funding
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MGenetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4MPersonalized Functional Genomics for Mitochondrial Encephalopathy Gene DiscoveryR01NS083726 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI BONNEN, PENELOPE E · 2014 to 2025
$6.1MComplete gene knockouts in autism: identification and functional characterizationR01MH113761 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI YU, TIMOTHY WEI-WEN · 2017 to 2021
$2.2MGene Discovery in Muscular DystrophyR01NS080929 · NINDS · UNIVERSITY OF FLORIDA · PI KANG, PETER B. · 2013 to 2017
$1.8MExpert Panel: Genetics of Malformations of the Central Nervous SystemU24HD093487 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI PODURI, ANNAPURNA, YU, TIMOTHY WEI-WEN · 2017 to 2019
$988kDepartment of HealthMedical Research Council G0800674NHGRI NIH HHS UM1 HG008900NICHD NIH HHS P50 HD105351NICHD NIH HHS U24 HD093487NIGMS NIH HHS T32 GM007748NIMH NIH HHS R01 MH113761NINDS NIH HHS R01 NS080929NINDS NIH HHS R01 NS083726Wellcome TrustWellcome Trust 203105/Z/16/Z
Abstract
While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism.
Indexed as
Transcription, GeneticAdolescentAdultChildDNA-Directed RNA PolymerasesDNA, MitochondrialFemaleFibroblastsHumansInfantMaleMitochondriaMutationNervous System DiseasesOxidative PhosphorylationPedigreeDNA-Directed RNA PolymerasesDNA, MitochondrialPOLRMT protein, humanProtein SubunitsRNA, Messenger
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