Asymmetric cell division requires specific mechanisms for adjusting global transcription

Abstract

Most cells divide symmetrically into two approximately identical cells. There are many examples, however, of asymmetric cell division that can generate sibling cell size differences. Whereas physical asymmetric division mechanisms and cell fate consequences have been investigated, the specific problem caused by asymmetric division at the transcription level has not yet been addressed. In symmetrically dividing cells the nascent transcription rate increases in parallel to cell volume to compensate it by keeping the actual mRNA synthesis rate constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this mechanism would provoke a never-ending increasing mRNA synthesis rate in smaller daughter cells. We show here that, contrarily to other eukaryotes with symmetric division, budding yeast keeps the nascent transcription rates of its RNA polymerases constant and increases mRNA stability. This control on RNA pol II-dependent transcription rate is obtained by controlling the cellular concentration of this enzyme.

Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast

“…We used a simplified protocol with TCA precipitation of the labelled nascent RNA into glass fibre filter discs (filter run-on: see M&M). Given that RNA pol II only accounts for 25% of the total nTR [1] and remains constant along the cell cycle [21] this result informs about RNA pol I+III nTR behaviour. Figure 1A shows that total nTR is constant in spite of a significant increase in cell volume.…”

“…In this scenario RNA pol II is limiting and cell volume increase is accompanied by the volume-dependent recruitment of RNA pol II onto target genes, as recently demonstrated in S. pombe [22]. In scenario #3 however, the S. cerevisiae RNA pol II nTR remains constant in spite of cell volume changes by changing the RNA pol II cell concentration to avoid changes in cell physiology along successive asymmetric cell divisions [21]. In scenario #2, the S. cerevisiae RNA pol I nTR also remains constant with cell volume, but via a different mechanism: nTR regulation by limiting RNA pol I targets.…”

“…The median values of the cell volumes of the population were obtained by a Coulter-Counter Z series device (Beckman Coulter, USA), as previously described [21]. The absolute values (in fL) are shown in Supplementary Table 1.…”

“…We have previously shown that the nTR for RNA pol II is regulated differently in cells presenting symmetrical or asymmetrical cell division [21]. In that study we proposed three models or scenarios for nTR regulation.…”

“…In a previous study [21], we used non-synchronised exponentially growing cultures of yeast strains with different average cell volumes. The set of strains included the wild-type haploid strain BY4741, two haploid mutants, cln3 and whi5, respectively with large and small volumes, and three polyploid (2n, 3n & 4n) strains created by D. Pellman's group [36] (with cell sizes of approximately 2x, 3X and 4X as regards BY4741).…”