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Translational activators and mitoribosomal isoforms cooperate to mediate mRNA-specific translation in Schizosaccharomyces pombe mitochondria
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2021-10-07 , DOI: 10.1093/nar/gkab789
Christopher J Herbert 1 , Sylvie Labarre-Mariotte 1 , David Cornu 1 , Cyrielle Sophie 1 , Cristina Panozzo 1 , Thomas Michel 1 , Geneviève Dujardin 1 , Nathalie Bonnefoy 1
Affiliation  

Mitochondrial mRNAs encode key subunits of the oxidative phosphorylation complexes that produce energy for the cell. In Saccharomyces cerevisiae, mitochondrial translation is under the control of translational activators, specific to each mRNA. In Schizosaccharomyces pombe, which more closely resembles the human system by its mitochondrial DNA structure and physiology, most translational activators appear to be either lacking, or recruited for post-translational functions. By combining bioinformatics, genetic and biochemical approaches we identified two interacting factors, Cbp7 and Cbp8, controlling Cytb production in S. pombe. We show that their absence affects cytb mRNA stability and impairs the detection of the Cytb protein. We further identified two classes of Cbp7/Cbp8 partners and showed that they modulated Cytb or Cox1 synthesis. First, two isoforms of bS1m, a protein of the small mitoribosomal subunit, that appear mutually exclusive and confer translational specificity. Second, a complex of four proteins dedicated to Cox1 synthesis, which includes an RNA helicase that interacts with the mitochondrial ribosome. Our results suggest that S. pombe contains, in addition to complexes of translational activators, a heterogeneous population of mitochondrial ribosomes that could specifically modulate translation depending on the mRNA translated, in order to optimally balance the production of different respiratory complex subunits.

中文翻译:

翻译激活剂和线粒体同种型协同介导粟酒裂殖酵母线粒体中的 mRNA 特异性翻译

线粒体 mRNA 编码为细胞产生能量的氧化磷酸化复合物的关键亚基。在 Saccharomyces cerevisiae 中,线粒体翻译受翻译激活剂的控制,特定于每个 mRNA。在粟酒裂殖酵母中,其线粒体 DNA 结构和生理学更类似于人类系统,大多数翻译激活剂似乎要么缺乏,要么被招募用于翻译后功能。通过结合生物信息学、遗传和生化方法,我们确定了两个相互作用的因子 Cbp7 和 Cbp8,它们控制着粟酒葡萄球菌中 Cytb 的产生。我们表明它们的缺失会影响 cytb mRNA 稳定性并损害 Cytb 蛋白的检测。我们进一步确定了两类 Cbp7/Cbp8 合作伙伴,并表明它们调节 Cytb 或 Cox1 合成。第一的,bS1m 的两种同工型,一种小线粒体亚基的蛋白质,它们看起来相互排斥并赋予翻译特异性。其次,一种由四种蛋白质组成的复合物,专门用于 Cox1 合成,其中包括一个与线粒体核糖体相互作用的 RNA 解旋酶。我们的研究结果表明,除了翻译激活剂的复合物外,庞贝酵母还含有异质的线粒体核糖体群,这些核糖体可以根据翻译的 mRNA 特异性调节翻译,以最佳地平衡不同呼吸复合物亚基的产生。其中包括与线粒体核糖体相互作用的 RNA 解旋酶。我们的研究结果表明,除了翻译激活剂的复合物外,庞贝酵母还含有异质的线粒体核糖体群,这些核糖体可以根据翻译的 mRNA 特异性调节翻译,以最佳地平衡不同呼吸复合物亚基的产生。其中包括与线粒体核糖体相互作用的 RNA 解旋酶。我们的研究结果表明,除了翻译激活剂的复合物外,庞贝酵母还含有异质的线粒体核糖体群,这些核糖体可以根据翻译的 mRNA 特异性调节翻译,以最佳地平衡不同呼吸复合物亚基的产生。
更新日期:2021-10-07
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