Autoregulation in the Biosynthesis of Ribosomes

Abstract

The synthesis of ribosomes in Saccharomyces cerevisiae consumes a prodigious amount of the cell's resources and, consequently, is tightly regulated. The rate of ribosome synthesis responds not only to nutritional cues but also to signals dependent on other macromolecular pathways of the cell, e.g., a defect in the secretory pathway leads to severe repression of transcription of both rRNA and ribosomal protein genes. A search for mutants that interrupted this repression revealed, surprisingly, that inactivation of RPL1B, one of a pair of genes encoding the 60S ribosomal protein L1, almost completely blocked the repression of rRNA and ribosomal protein gene transcription that usually follows a defect in the secretory pathway. Further experiments showed that almost any mutation leading to a defect in 60S subunit synthesis had the same effect, whereas mutations affecting 40S subunit synthesis did not. Although one might suspect that this effect would be due to a decrease in the initiation of translation or to the presence of half-mers, i.e., polyribosomes awaiting a 60S subunit, our data show that this is not the case. Rather, a variety of experiments suggest that some aspect of the production of defective 60S particles or, more likely, their breakdown suppresses the signal generated by a defect in the secretory pathway that represses ribosome synthesis.

ACKNOWLEDGMENTS

We are grateful to U. Maitra, J. Woolford, A. Johnson, and P. Silver for strains and to I. Willis and C. Query for careful readings of the manuscript.

This work was supported in part by grant GM25532 to J.R.W. and grant CA13330 to the Albert Einstein Cancer Center and by a Human Frontiers grant to J.R.W.