The DEAD-box helicase Mss116 plays distinct roles in mitochondrial ribogenesis and mRNA-specific translation.
The DEAD-box helicase Mss116 plays distinct roles in mitochondrial ribogenesis and mRNA-specific translation.
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DOI：
10.1093/nar/gkx426
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发表时间：
2017-06-20
影响因子：
14.9
通讯作者：
Barrientos A
中科院分区：
文献类型：
--
作者：
De Silva D;Poliquin S;Zeng R;Zamudio-Ochoa A;Marrero N;Perez-Martinez X;Fontanesi F;Barrientos A
DEAD-box家族的成员通常是参与多种RNA交易的多功能蛋白质。其中，酵母Saccharomyces cerevisiae Mss116参与线粒体内含子剪接，在冷胁迫下也参与线粒体转录伸长。在这里，我们发现Mss116与线粒体组装因子Mrh4相互作用，是有效的线粒体生物发生所必需的，因此，维持线粒体蛋白质的整体合成速率。此外，Mss116是有效的COX1 mRNA翻译起始和延伸所必需的。Mss116与COX1 mrna特异性翻译激活因子Pet309相互作用。在缺乏Mss116的情况下，Pet309实际上是不存在的，尽管可以发生线粒体装载到COX1 mRNA上，但COX1 mRNA翻译的激活受到损害。取消Mss116解旋酶活性的突变不会阻止Mss116与Pet309的相互作用，但也不允许COX1 mRNA翻译。我们提出Pet309作为Mss116作用于COX1 mRNA 5΄-UTR的衔接蛋白，促进COX1的高效合成。总之，我们得出结论，Mss116在生物发生和线粒体翻译机制中的不同功能取决于Mss116与其蛋白辅因子的相互作用。
Members of the DEAD-box family are often multifunctional proteins involved in several RNA transactions. Among them, yeast Saccharomyces cerevisiae Mss116 participates in mitochondrial intron splicing and, under cold stress, also in mitochondrial transcription elongation. Here, we show that Mss116 interacts with the mitoribosome assembly factor Mrh4, is required for efficient mitoribosome biogenesis, and consequently, maintenance of the overall mitochondrial protein synthesis rate. Additionally, Mss116 is required for efficient COX1 mRNA translation initiation and elongation. Mss116 interacts with a COX1 mRNA-specific translational activator, the pentatricopeptide repeat protein Pet309. In the absence of Mss116, Pet309 is virtually absent, and although mitoribosome loading onto COX1 mRNA can occur, activation of COX1 mRNA translation is impaired. Mutations abolishing the helicase activity of Mss116 do not prevent the interaction of Mss116 with Pet309 but also do not allow COX1 mRNA translation. We propose that Pet309 acts as an adaptor protein for Mss116 action on the COX1 mRNA 5΄-UTR to promote efficient Cox1 synthesis. Overall, we conclude that the different functions of Mss116 in the biogenesis and functioning of the mitochondrial translation machinery depend on Mss116 interplay with its protein cofactors.