Format

Send to

Choose Destination
Cell Syst. 2018 Jan 24;6(1):125-135.e6. doi: 10.1016/j.cels.2017.11.012. Epub 2017 Dec 13.

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

Author information

1
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
2
Morgridge Institute for Research, Madison, WI 53715, USA.
3
Genome Center of Wisconsin, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
4
Genome Center of Wisconsin, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
5
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: wickens@biochem.wisc.edu.
6
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Morgridge Institute for Research, Madison, WI 53715, USA. Electronic address: dpagliarini@morgridge.org.

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 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.

KEYWORDS:

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

PMID:
29248374
PMCID:
PMC5799006
DOI:
10.1016/j.cels.2017.11.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center