Rozanska Agata, Richter-Dennerlein Ricarda, Rorbach Joanna, Gao Fei, Lewis Richard J, Chrzanowska-Lightowlers Zofia M, Lightowlers Robert N
Institute for Cell and Molecular Bioscience, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, U.K.
The Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, U.K.
Biochem J. 2017 Jun 13;474(13):2145-2158. doi: 10.1042/BCJ20170256.
Accurate assembly and maturation of human mitochondrial ribosomes is essential for synthesis of the 13 polypeptides encoded by the mitochondrial genome. This process requires the correct integration of 80 proteins, 1 mt (mitochondrial)-tRNA and 2 mt-rRNA species, the latter being post-transcriptionally modified at many sites. Here, we report that human ribosome-binding factor A (RBFA) is a mitochondrial RNA-binding protein that exerts crucial roles in mitoribosome biogenesis. Unlike its bacterial orthologue, RBFA associates mainly with helices 44 and 45 of the 12S rRNA in the mitoribosomal small subunit to promote dimethylation of two highly conserved consecutive adenines. Characterization of RBFA-depleted cells indicates that this dimethylation is not a prerequisite for assembly of the small ribosomal subunit. However, the RBFA-facilitated modification is necessary for completing mt-rRNA maturation and regulating association of the small and large subunits to form a functional monosome implicating RBFA in the quality control of mitoribosome formation.
人线粒体核糖体的精确组装和成熟对于线粒体基因组编码的13种多肽的合成至关重要。这一过程需要80种蛋白质、1种线粒体（mt）-tRNA和2种mt-rRNA的正确整合，后两者在多个位点进行转录后修饰。在此，我们报道人核糖体结合因子A（RBFA）是一种线粒体RNA结合蛋白，在线粒体核糖体生物发生中发挥关键作用。与其细菌同源物不同，RBFA主要与线粒体核糖体小亚基中12S rRNA的44和45螺旋结合，以促进两个高度保守的连续腺嘌呤的二甲基化。对RBFA缺失细胞的表征表明，这种二甲基化不是小核糖体亚基组装的先决条件。然而，RBFA促进的修饰对于完成mt-rRNA成熟以及调节小亚基和大亚基的结合以形成功能性单体是必要的，这表明RBFA参与了线粒体核糖体形成的质量控制。
