Methylation of 12S rRNA Is Necessary for In Vivo Stability of the Small Subunit of the Mammalian Mitochondrial Ribosome
Methylation of 12S rRNA Is Necessary for In Vivo Stability of the Small Subunit of the Mammalian Mitochondrial Ribosome
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DOI：
10.1016/j.cmet.2009.03.001
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发表时间：
2009-04-08
期刊：
影响因子：
29
通讯作者：
Larsson, Nils-Goeran
中科院分区：
文献类型：
--
作者：
Metodiev, Metodi D.;Lesko, Nicole;Larsson, Nils-Goeran
核糖体小亚基的rRNA的3'端含有两个高度保守的二甲基化腺嘌呤。这种修饰和负责的甲基转移酶存在于生命的所有三个领域，但其功能仍然难以捉摸。我们已经破坏了小鼠TFB1M，基因编码的线粒体蛋白同源的细菌二甲基转移酶，并在这里证明，TFB1M的损失是胚胎致死。心脏中Tfb1m的破坏导致线粒体核糖体小亚基的rRNA的腺嘌呤二甲基化的完全丧失，线粒体核糖体的组装受损，并且线粒体翻译被废除。此外，我们目前的生化证据表明，TFB1M不激活或抑制转录TFB2M的存在。因此，我们的研究结果表明，TFB1M是一个非冗余的二甲基转移酶在哺乳动物线粒体。此外，我们提供了一个可能的解释普遍保守的腺嘌呤二甲基化的核糖体的维护显示一个关键的作用。
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.