Delayed rRNA processing results in significant ribosome biogenesis and functional defects

Arturas Meskauskas1, Jennifer L Baxter, Edward A Carr

  • 1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.

Insights

The histone deacetylase RPD3 controls ribosomal frameshifting and virus stability in yeast. Its loss causes ribosome defects, increasing frameshifting and impacting virus maintenance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The mof6-1 mutation in Saccharomyces cerevisiae affects programmed -1 ribosomal frameshifting and killer virus maintenance.
  • Histone deacetylases play crucial roles in gene regulation and cellular processes.

Purpose of the Study:

  • To identify the gene responsible for the mof6-1 mutation.
  • To elucidate the role of histone deacetylase RPD3 in ribosomal frameshifting and virus maintenance.
  • To investigate the mechanism by which RPD3 influences ribosome function.

Main Methods:

  • Genetic analysis of the mof6-1 mutation in yeast.
  • Complementation studies using the human homolog of RPD3.
  • Analysis of rRNA processing and ribosome activity in wild-type and mutant strains.

Main Results:

  • The mof6-1 mutation is an allele of the histone deacetylase gene RPD3.
  • RPD3's deacetylase function is essential for normal ribosomal frameshifting and killer virus stability.
  • Loss of RPD3 function leads to delayed rRNA processing, producing ribosomes with altered tRNA affinities and reduced peptidyltransferase activity.
  • The human homolog of RPD3 can rescue these yeast defects.

Conclusions:

  • RPD3-mediated histone deacetylation is critical for proper ribosome biogenesis and function.
  • Defects in rRNA processing and ribosome activity underlie the increased frameshifting efficiencies observed in rpd3 mutants.
  • These findings highlight a conserved role for histone deacetylases in regulating translation fidelity and viral stability.

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