PMID- 29248374 OWN - NLM STAT- MEDLINE DCOM- 20190923 LR - 20200306 IS - 2405-4712 (Print) IS - 2405-4720 (Electronic) IS - 2405-4712 (Linking) VI - 6 IP - 1 DP - 2018 Jan 24 TI - Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis. PG - 125-135.e6 LID - S2405-4712(17)30540-9 [pii] LID - 10.1016/j.cels.2017.11.012 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Lapointe, Christopher P AU - Lapointe CP AD - Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Stefely, Jonathan A AU - Stefely JA AD - Morgridge Institute for Research, Madison, WI 53715, USA. FAU - Jochem, Adam AU - Jochem A AD - Morgridge Institute for Research, Madison, WI 53715, USA. FAU - Hutchins, Paul D AU - Hutchins PD AD - Genome Center of Wisconsin, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Wilson, Gary M AU - Wilson GM AD - Genome Center of Wisconsin, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Kwiecien, Nicholas W AU - Kwiecien NW AD - Genome Center of Wisconsin, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Coon, Joshua J AU - Coon JJ AD - 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. FAU - Wickens, Marvin AU - Wickens M AD - Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: wickens@biochem.wisc.edu. FAU - Pagliarini, David J AU - Pagliarini DJ AD - Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Morgridge Institute for Research, Madison, WI 53715, USA. Electronic address: dpagliarini@morgridge.org. LA - eng GR - F30 AG043282/AG/NIA NIH HHS/United States GR - R01 GM112057/GM/NIGMS NIH HHS/United States GR - T32 GM008692/GM/NIGMS NIH HHS/United States GR - R35 GM118110/GM/NIGMS NIH HHS/United States GR - R01 GM050942/GM/NIGMS NIH HHS/United States GR - T32 GM008349/GM/NIGMS NIH HHS/United States GR - R01 GM115591/GM/NIGMS NIH HHS/United States GR - P41 GM108538/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20171213 PL - United States TA - Cell Syst JT - Cell systems JID - 101656080 RN - 0 (PUF3 protein, S cerevisiae) RN - 0 (RNA-Binding Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 1339-63-5 (Ubiquinone) SB - IM MH - Mitochondria/enzymology MH - Organelle Biogenesis MH - Oxidative Phosphorylation MH - RNA-Binding Proteins/*genetics/*metabolism MH - Saccharomyces cerevisiae/enzymology/genetics MH - Saccharomyces cerevisiae Proteins/*genetics/*metabolism MH - Ubiquinone/biosynthesis PMC - PMC5799006 MID - NIHMS922863 OTO - NOTNLM OT - *COQ5 OT - *PUF3 OT - *RNA binding protein OT - *biogenesis OT - *coenzyme Q OT - *complex Q OT - *mitochondria OT - *multi-omic OT - *transomic OT - *ubiquinone EDAT- 2017/12/19 06:00 MHDA- 2019/09/24 06:00 PMCR- 2019/01/24 CRDT- 2017/12/18 06:00 PHST- 2017/05/31 00:00 [received] PHST- 2017/09/14 00:00 [revised] PHST- 2017/11/19 00:00 [accepted] PHST- 2017/12/19 06:00 [pubmed] PHST- 2019/09/24 06:00 [medline] PHST- 2017/12/18 06:00 [entrez] PHST- 2019/01/24 00:00 [pmc-release] AID - S2405-4712(17)30540-9 [pii] AID - 10.1016/j.cels.2017.11.012 [doi] PST - ppublish SO - Cell Syst. 2018 Jan 24;6(1):125-135.e6. doi: 10.1016/j.cels.2017.11.012. Epub 2017 Dec 13.