Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Morgridge Institute for Research, Madison, WI 53715, USA.
Cell Syst. 2018 Jan 24;6(1):125-135.e6. doi: 10.1016/j.cels.2017.11.012. Epub 2017 Dec 13.
Coenzyme Q (CoQ) is a redox-active lipid required for mitochondrial oxidative phosphorylation (OxPhos). How CoQ biosynthesis is coordinated with the biogenesis of OxPhos protein complexes is unclear. Here, we show that the Saccharomyces cerevisiae RNA-binding protein (RBP) Puf3p regulates CoQ biosynthesis. To establish the mechanism for this regulation, we employed a multi-omic strategy to identify mRNAs that not only bind Puf3p but also are regulated by Puf3p in vivo. The CoQ biosynthesis enzyme Coq5p is a critical Puf3p target: Puf3p regulates the abundance of Coq5p and prevents its detrimental hyperaccumulation, thereby enabling efficient CoQ production. More broadly, Puf3p represses a specific set of proteins involved in mitochondrial protein import, translation, and OxPhos complex assembly (pathways essential to prime mitochondrial biogenesis). Our data reveal a mechanism for post-transcriptionally coordinating CoQ production with OxPhos biogenesis, and they demonstrate the power of multi-omics for defining genuine targets of RBPs.
辅酶 Q（CoQ）是一种氧化还原活性脂质，是线粒体氧化磷酸化（OxPhos）所必需的。辅酶 Q 生物合成如何与 OxPhos 蛋白复合物的生物发生协调尚不清楚。在这里，我们表明酿酒酵母 RNA 结合蛋白（RBP）Puf3p 调节辅酶 Q 生物合成。为了确定这种调节的机制，我们采用了一种多组学策略来鉴定不仅与 Puf3p 结合，而且在体内受 Puf3p 调节的 mRNA。辅酶 Q 生物合成酶 Coq5p 是 Puf3p 的一个关键靶标：Puf3p 调节 Coq5p 的丰度并防止其有害的过度积累，从而能够有效地产生辅酶 Q。更广泛地说，Puf3p 抑制一组特定的与线粒体蛋白输入、翻译和 OxPhos 复合物组装（对启动线粒体生物发生至关重要的途径）相关的蛋白质。我们的数据揭示了一种转录后协调辅酶 Q 产生与 OxPhos 生物发生的机制，并证明了多组学在定义 RBP 的真正靶标的强大功能。
