ArticleHuman molecular genetics2017
Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Review
- [Decreased plasma citrulline is a biochemical marker in newborn screening forZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk.Nature communications · 2024Article
- Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.Frontiers in cell and developmental biology · 2024Review
- TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease.Nature communications · 2023Article
- Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models.International journal of molecular sciences · 2023Review
- The role of m5C methyltransferases in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Review
- Mitochondrial rRNA Methylation by Mettl15 Contributes to the Exercise and Learning Capability in Mice.International journal of molecular sciences · 2022Article
- Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases.Cell & bioscience · 2022Review
- A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.Nature communications · 2022Article
- Mitochondrial noncoding RNAs: new wine in an old bottle.RNA biology · 2021Review
- Review
- Article
- The role of OncoSnoRNAs and Ribosomal RNA 2'-O-methylation in Cancer.RNA biology · 2021Review
- Brain-trait-associated variants impact cell-type-specific gene regulation during neurogenesis.American journal of human genetics · 2021Article
- Structural basis for late maturation steps of the human mitoribosomal large subunit.Nature communications · 2021Article
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria.Nucleic acids research · 2021Article
- Contribution of nuclear and mitochondrial gene mutations in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.Journal of neurology · 2021Article
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
Defects in nuclear-encoded proteins of the mitochondrial translation machinery cause early-onset and tissue-specific deficiency of one or more OXPHOS complexes. Here, we report a 7-year-old Italian boy with childhood-onset rapidly progressive encephalomyopathy and stroke-like episodes. Multiple OXPHOS defects and decreased mtDNA copy number (40%) were detected in muscle homogenate. Clinical features combined with low level of plasma citrulline were highly suggestive of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, however, the common m.3243 A > G mutation was excluded. Targeted exome sequencing of genes encoding the mitochondrial proteome identified a damaging mutation, c.567 G > A, affecting a highly conserved amino acid residue (p.Gly189Arg) of the MRM2 protein. MRM2 has never before been linked to a human disease and encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA. We generated a knockout yeast model for the orthologous gene that showed a defect in respiration and the reduction of the 2'-O-methyl modification at the equivalent position (U2791) in the yeast mitochondrial 21S rRNA. Complementation with the mrm2 allele carrying the equivalent yeast mutation failed to rescue the respiratory phenotype, which was instead completely rescued by expressing the wild-type allele. Our findings establish that defective MRM2 causes a MELAS-like phenotype, and suggests the genetic screening of the MRM2 gene in patients with a m.3243 A > G negative MELAS-like presentation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.