Altered patterns of ribonucleic acid synthesis during the cell cycle: a mechanism compensating for variation in gene concentration.

In the fission yeast Schizosaccharomyces pombe, a series of diploid mutants divides at smaller cell sizes than wild type. In these smaller strains, the mean gene concentration (defined by previous authors as the DNA to protein ratio) is higher than in wild type. Such an increase in gene concentration should also increase the concentration of those components such as messenger and ribosomal RNA, whose rate of synthesis is determined by gene dosage. We show that the mean concentrations of these 2 RNA species in the small cells are not increased, but are the same as in wild type. The small mutant cells are thus able to compensate for changes in gene concentration. This compensation is shown to operate through differences in the patterns of synthesis of RNA during the cell cycle. In all the strains of the diploid series, the rates of synthesis of messenger and ribosomal RNA double as steps once in each cell cycle. The timings of the steps in the cell cycle appear to be cell-size related, since the smaller the cell at division, the later are the steps in the cell cycle. In contrast, there is comparatively little variation in the timing of DNA replication in the cycles of cells of different sizes. We propose that after DNA replication, there is a delay before doubling in the rate of transcription. Such a cell mass-related delay is all that is required to compensate for increased gene concentration, and results in the same mean functional DNA concentration in all strains. This mechanism will maintain the same mean messenger and ribosomal RNA concentrations in cells dividing at different sizes. Ways in which the cell size-related control over transcription may operate are discussed.