Vanillin inhibits translation and induces messenger ribonucleoprotein (mRNP) granule formation in saccharomyces cerevisiae: application and validation of high-content, image-based profiling

PLoS One. 2013 Apr 24;8(4):e61748. doi: 10.1371/journal.pone.0061748. Print 2013.

Abstract

Vanillin, generated by acid hydrolysis of lignocellulose, acts as a potent inhibitor of the growth of the yeast Saccharomyces cerevisiae. Here, we investigated the cellular processes affected by vanillin using high-content, image-based profiling. Among 4,718 non-essential yeast deletion mutants, the morphology of those defective in the large ribosomal subunit showed significant similarity to that of vanillin-treated cells. The defects in these mutants were clustered in three domains of the ribosome: the mRNA tunnel entrance, exit and backbone required for small subunit attachment. To confirm that vanillin inhibited ribosomal function, we assessed polysome and messenger ribonucleoprotein granule formation after treatment with vanillin. Analysis of polysome profiles showed disassembly of the polysomes in the presence of vanillin. Processing bodies and stress granules, which are composed of non-translating mRNAs and various proteins, were formed after treatment with vanillin. These results suggest that vanillin represses translation in yeast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzaldehydes / pharmacology*
  • Cytoplasmic Granules / metabolism*
  • Ergosterol / biosynthesis
  • Models, Molecular
  • Molecular Conformation
  • Mutation
  • Polyribosomes / metabolism
  • Protein Transport / drug effects
  • Ribonucleoproteins / metabolism*
  • Ribosome Subunits, Large / chemistry
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*

Substances

  • Benzaldehydes
  • Ribonucleoproteins
  • messenger ribonucleoprotein
  • vanillin
  • Ergosterol

Grants and funding

This work was supported by the New Energy and Industrial Technology Development Organization (Y.O.) and by grants for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (24370002 to Y.O. and 23580113 to S. I.). S.O. was a research fellow of the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.