Yeast Genetics and Molecular Biology 2000
University of Washington
Seattle, Washington USA
July 2000


Name: Culbertson, Michael
Mailing Address: Genetics, University of Wisconsin, 1535 Linden Drive, Madison, WI 53706, USA
Email Address: mrculber@facstaff.wisc.edu
Phone & FAX numbers: 608-262-5388 & 608-262-4570

#046

Autoregulation of ribosomal protein synthesis.
Michael Culbertson, Doris Ursic, James Hendrick
Genetics, University of Wisconsin, 1535 Linden Drive, Madison, WI 53706, USA

In bacteria, ribosomal protein synthesis is regulated by translational repression. Regulatory r-proteins bind to their own mRNAs to prevent translation and/or promote mRNA decay when they are not bound in ribosomes. No equivalent mechanism has been found in yeast for controlling r-protein abundance, although several r-proteins have been shown to autoregulate their own synthesis. We identified an autoregulatory system controlling the expression of SUF14 (RPS3), which codes for ribosomal protein S3. Analyzing the effects of increased gene dosage on mRNA accumulation revealed that expression was regulated. We found that S3 inhibits its own synthesis by limiting the accumulation of SUF14 mRNA, suggesting that regulation may be mediated either through a change in the rate of mRNA transcription or through a change in the rate of mRNA decay. A frameshift mutation in SUF14 that blocks translation eliminated regulation, indicating that S3 is required for regulation. Experiments with a fusion of the CUP1 promoter to the SUF14 ORF confirmed this conclusion and also indicated that either the promoter and/or the 5'-UTR of SUF14 is required for regulation. Using a SUF14placZ fusion, run-on transcription assays, and estimates of mRNA half-life, our results suggest that the 5'-UTR is necessary but not sufficient for regulation. Transcription appears to play a minor role if any in regulation. S3-mediated changes in mRNA decay rate may be the primary mechanism for regulation.


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