Decoupling of Cell Volume From the Number of Ribosomal DNA Repeat Copies Through Regulation of RNA Polymerase I Transcription Elongation in a Large‐Cell Yeast Mutant

Although most studies in the regulation of gene transcription in eukaryotes have focused on protein-coding genes transcribed into mRNA by RNA polymerase II, the regulation of RNA polymerase I (RNA Pol I) transcription is a key step in the cell's adaptation to environmental or physiological changes. This polymerase transcribes rRNA, a fundamental component of ribosomes that controls the translation of mRNAs into proteins-macromolecules that are both highly abundant and energetically costly to synthesize. Using the yeast Saccharomyces cerevisiae as a model, we have previously shown that adaptation of RNA Pol I synthesis rate (SR) to large changes in cell volume exhibited by some mutants, such as cln3, occurs over the long term through amplification of rDNA gene copies across several hundred cell divisions. However, it remains unclear what happens in the short term in de novo generated mutants that do not display rDNA amplification but exhibit all other phenotypic characteristics of the evolved cln3 mutant. Here, using an in vivo labeling procedure, we show that the RNA Pol I SR is similar in de novo and evolved cln3 mutants and that it seems not to be an alteration in the proportion of active rDNA copies or rRNA processing between both cln3 mutants. Finally, by measuring the ratio of active elongating RNA Pol I molecules to the total loaded onto rDNA genes, we conclude that short-term adaptation occurs through an increase in their transcription efficiency that compensates the decrease in the total number of elongating RNA polymerases.