COUPLING OF CELL-DIVISION TO CELL-GROWTH BY TRANSLATIONAL CONTROL OF THE G(1) CYCLIN CLN3 IN YEAST

The eukaryotic cell cycle is driven by a cascade of cyclins and kinase partners including the G(1) cyclin Cln3p in yeast. As the first step in this cascade, Cln3p is uniquely positioned to determine the critica l growth-rate threshold for division. To analyze factors regulating CL N3 expression, we identified a short upstream open reading frame (uORF ) in the 5' leader of CLN3 mRNA as a translational control element. Th is control element is critical for the growth-dependent regulation of Cln3p synthesis because it specifically represses CLN3 expression duri ng conditions of diminished protein synthesis or slow growth. Inactiva tion of the uORF accelerates the completion of Start and entry into th e fell cycle suggesting that translational regulation of CLN3 provides a mechanism coupling cell growth and division.