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A more recent version of this article appeared on March 1, 2007
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Submitted on June 9, 2006
Revised on December 5, 2006
Accepted on December 20, 2006
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Departments of Molecular Biophysics and Biochemistry, *Genetics, and ||Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520; Rockefeller University, New York, NY 10021
Monitoring Editor: Karsten Weis
In the yeast S. cerevisiae it has long been thought that cells must reach a critical cell size, called the ‘setpoint’, in order to allow the Start cell cycle transition. Recent evidence suggests that this setpoint is lowered when ribosome biogenesis is slowed. Here we present evidence that yeast can sense ribosome biogenesis independently of mature ribosome levels and protein synthetic capacity. Our results suggest that ribosome biogenesis directly promotes passage through Start through Whi5, the yeast functional equivalent to the human tumor suppressor Rb. When ribosome biogenesis is inhibited, a Whi5 dependent mechanism inhibits passage through Start before significant decreases in both the number of ribosomes and in overall translation capacity of the cell become evident. This delay at Start in response to decreases in ribosome biogenesis occurs independently of Cln3, the major known Whi5 antagonist. Thus ribosome biogenesis may be sensed at multiple steps in Start regulation. Ribosome biogenesis may thus both delay Start by increasing the cell size setpoint, and independently may promote Start by inactivating Whi5.
These authors contributed equally to this work.
Address correspondence to:
Susan J. Baserga (susan.baserga{at}yale.edu)
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