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Methylation of 12S rRNA i… - University of Gothenburg, Sweden Till startsida
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Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome.

Journal article
Authors Metodi D Metodiev
Nicole Lesko
Chan Bae Park
Yolanda Cámara
Yonghong Shi
Rolf Wibom
Kjell Hultenby
Claes M Gustafsson
Nils-Göran Larsson
Published in Cell metabolism
Volume 9
Issue 4
Pages 386-97
ISSN 1932-7420
Publication year 2009
Published at
Pages 386-97
Language en
Keywords Animals, Cardiomyopathies, metabolism, pathology, DNA, Mitochondrial, genetics, Electron Transport, Embryonic Development, Gene Expression Regulation, Developmental, Mammals, metabolism, Methylation, Mice, Mice, Knockout, Mitochondria, genetics, metabolism, ultrastructure, Myocardium, pathology, ultrastructure, Organ Specificity, Protein Biosynthesis, RNA, Messenger, genetics, metabolism, RNA, Ribosomal, metabolism, Ribosome Subunits, Small, Eukaryotic, metabolism, Transcription Factors, deficiency, genetics, metabolism, Transcription, Genetic
Subject categories Chemistry


The 3' end of the rRNA of the small ribosomal subunit contains two extremely highly conserved dimethylated adenines. This modification and the responsible methyltransferases are present in all three domains of life, but its function has remained elusive. We have disrupted the mouse Tfb1m gene encoding a mitochondrial protein homologous to bacterial dimethyltransferases and demonstrate here that loss of TFB1M is embryonic lethal. Disruption of Tfb1m in heart leads to complete loss of adenine dimethylation of the rRNA of the small mitochondrial ribosomal subunit, impaired assembly of the mitochondrial ribosome, and abolished mitochondrial translation. In addition, we present biochemical evidence that TFB1M does not activate or repress transcription in the presence of TFB2M. Our results thus show that TFB1M is a nonredundant dimethyltransferase in mammalian mitochondria. In addition, we provide a possible explanation for the universal conservation of adenine dimethylation of rRNA by showing a critical role in ribosome maintenance.

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