Post-Transcriptional Control of Coenzyme Q Biosynthesis Revealed by Transomic Analysis of the RNA-Binding Protein Puf3p

Abstract

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 directly regulates CoQ biosynthesis. To establish the mechanism for this regulation, we employed a transomic 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 Put3p target: Puf3p regulates the level of Coq5p and prevents its toxicity, thereby enabling efficient CoQ production. In parallel, 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, more broadly, demonstrate the power of transomics for defining genuine targets of RBPs.\n\nHIGHLIGHTSO_LIThe RNA binding protein (RBP) Puf3p regulates coenzyme Q (CoQ) biosynthesis\nC_LIO_LITransomic analysis of RNAs, proteins, lipids, and metabolites defines RBP targets\nC_LIO_LIPuf3p regulates the potentially toxic CoQ biosynthesis enzyme Coq5p\nC_LIO_LIPuf3p couples regulation of CoQ with a broader program for controlling mitochondria\nC_LI