Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast

J Biol Chem. 2017 Sep 8;292(36):14851-14866. doi: 10.1074/jbc.M117.798397. Epub 2017 Jul 24.

Abstract

Despite its relatively streamlined genome, there are many important examples of regulated RNA splicing in Saccharomyces cerevisiae Here, we report a role for the chromatin remodeler SWI/SNF in respiration, partially via the regulation of splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a mitochondrial phosphatase regulator of biosynthesis of coenzyme Q6 (ubiquinone or CoQ6) and a mitochondrial redox-active lipid essential for electron and proton transport in respiration. Increased splicing of PTC7 increases CoQ6 levels. The increase in PTC7 splicing occurs at least in part due to down-regulation of ribosomal protein gene expression, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to otherwise poorly spliced transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7 represses CoQ6 biosynthesis. Taken together, these findings uncover a link between Snf2 expression and the splicing of PTC7 and establish a previously unknown role for the SWI/SNF complex in the transition of yeast cells from fermentative to respiratory modes of metabolism.

Keywords: Saccharomyces cerevisiae; alternative splicing; chromatin remodeling; coenzyme Q; gene expression; lipid metabolism; metabolic regulation; mitochondrial metabolism; phosphorylation.

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Chromatin / metabolism*
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism*
  • RNA Splicing / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Ubiquinone / biosynthesis*

Substances

  • Chromatin
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • ubiquinone 6
  • Ubiquinone
  • PTC7 protein, S cerevisiae
  • Protein Phosphatase 2
  • Adenosine Triphosphatases
  • SNF2 protein, S cerevisiae