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Molecular and Cellular Biology, March 2003, p. 1602-1613, Vol. 23, No. 5
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.5.1602-1613.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Delayed rRNA Processing Results in Significant Ribosome Biogenesis and Functional Defects

Arturas Meskauskas,1 Jennifer L. Baxter,1 Edward A. Carr,2 Jason Yasenchak,2 Jennifer E. G. Gallagher,3 Susan J. Baserga,3 and Jonathan D. Dinman1*

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, 20742,1 Graduate School of Biomedical Sciences, Rutgers University and The University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854,2 Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, Connecticut 06520-80243

Received 3 October 2002/ Returned for modification 25 November 2002/ Accepted 12 December 2002

mof6-1 was originally isolated as a recessive mutation in Saccharomyces cerevisiae which promoted increased efficiencies of programmed -1 ribosomal frameshifting and rendered cells unable to maintain the killer virus. Here, we demonstrate that mof6-1 is a unique allele of the histone deacetylase RPD3, that the deacetylase function of Rpd3p is required for controlling wild-type levels of frameshifting and virus maintenance, and that the closest human homolog can fully complement these defects. Loss of the Rpd3p-associated histone deacetylase function, either by mutants of rpd3 or loss of the associated gene product Sin3p or Sap30p, results in a delay in rRNA processing rather than in an rRNA transcriptional defect. This results in production of ribosomes having lower affinities for aminoacyl-tRNA and diminished peptidyltransferase activities. We hypothesize that decreased rates of peptidyl transfer allow ribosomes with both A and P sites occupied by tRNAs to pause for longer periods of time at -1 frameshift signals, promoting increased programmed -1 ribosomal frameshifting efficiencies and subsequent loss of the killer virus. The frameshifting defect is accentuated when the demand for ribosomes is highest, suggesting that rRNA posttranscriptional modification is the bottleneck in ribosome biogenesis.

* Corresponding author. Mailing address: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742. Phone: (301) 405-0918. Fax: (301) 314-9489. E-mail: jd280{at}umail.umd.edu.

Molecular and Cellular Biology, March 2003, p. 1602-1613, Vol. 23, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.5.1602-1613.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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