Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis

Christopher P. Lapointe, Jonathan A. Stefely, Adam Jochem, Paul D. Hutchins, Gary M. Wilson, Nicholas W. Kwiecien, Joshua J. Coon, Marvin Wickens, David J. Pagliarini

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


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. Mitochondrial biogenesis demands the coordinated integration of metabolites, lipids, and proteins encoded by two genomes into functional organelles. Although transcription factors for this process have been identified, roles of post-transcriptional regulators remain poorly defined. Using a “multi-omic” approach that incorporates measurements of mRNAs, proteins, lipids, and metabolites, we reveal the consequences of regulation by a yeast RNA-binding protein across four “omic” planes. Our data identify a mechanism for the post-transcriptional coordination of mitochondrial coenzyme Q and protein synthesis and demonstrate the power of multi-omics to identify genuine targets and cellular functions of RNA-binding proteins.

Original languageEnglish
Pages (from-to)125-135.e6
JournalCell Systems
Issue number1
StatePublished - Jan 24 2018


  • COQ5
  • PUF3
  • RNA binding protein
  • biogenesis
  • coenzyme Q
  • complex Q
  • mitochondria
  • multi-omic
  • transomic
  • ubiquinone


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