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Journal of Bacteriology, March 1999, p. 1793-1800, Vol. 181, No. 6
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Uracil-Induced Down-Regulation of the Yeast Uracil Permease

Karin Séron,dagger Marie-Odile Blondel, Rosine Haguenauer-Tsapis, and Christiane Volland*

Institut Jacques Monod, CNRS/Université Paris 7---Denis Diderot 2, 75251 Paris Cedex 05, France

Received 30 September 1998/Accepted 12 January 1999

In Saccharomyces cerevisiae the FUR4-encoded uracil permease catalyzes the first step of the pyrimidine salvage pathway. The availability of uracil has a negative regulatory effect upon its own transport. Uracil causes a decrease in the level of uracil permease, partly by decreasing the FUR4 mRNA level in a promoter-independent fashion, probably by increasing its instability. Uracil entry also triggers more rapid degradation of the existing permease by promoting high efficiency of ubiquitination of the permease that signals its internalization. A direct binding of intracellular uracil to the permease is possibly involved in this feedback regulation, as the behavior of the permease is similar in mutant cells unable to convert intracellular uracil into UMP. We used cells impaired in the ubiquitination step to show that the addition of uracil produces rapid inhibition of uracil transport. This may be the first response prior to the removal of the permease from the plasma membrane. Similar down-regulation of uracil uptake, involving several processes, was observed under adverse conditions mainly corresponding to a decrease in the cellular content of ribosomes. These results suggest that uracil of exogenous or catabolic origin down-regulates the cognate permease to prevent buildup of excess intracellular uracil-derived nucleotides.

* Corresponding author. Mailing address: Institut Jacques Monod, CNRS/Université Paris 7-Denis Diderot, 2, Place Jussieu, 75251 Paris Cedex 05, France. Phone: 33 1 44 27 47 24. Fax: 33 1 44 27 59 94. E-mail: volland{at}ijm.jussieu.fr.

dagger Present address: Laboratoire de Biologie et Biochimie parasitaires et fongiques, 369, rue Jules Guesde, 59651-Villeneuve d'Ascq, France.

Journal of Bacteriology, March 1999, p. 1793-1800, Vol. 181, No. 6
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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