Scaling of Transcript Abundance with Cell Size and the Commitment to Cell Division

Abstract: All cells must grow to a minimum size—the “critical size”—before they can commit to cell division. This size requirement prevents cells from becoming too big or too small, and it co- ordinates division with the availability of nutrients and cell growth in mass. As a consequence of size control, cells have narrow and characteristic distributions of cell size. Despite decades of study, it is unknown how cells measure and respond to size, or why mechanistically a minimum size is required for commitment to division. We have recently discovered that as G1 phase yeast cells grow in size, several hundred mRNAs are systematically expressed at higher and higher levels—they increase faster than the increase in size, and increase in concentration. Other mRNAs do the opposite—they increase slower than the increase in size, and so decrease in concentration. Strikingly, genes that activate the cell cycle fall into the first group, while genes that inhibit the cell cycle fall into the second group. This suggests that the ratio of activators to inhibitors increases as G1 phase cells grow, and that it is achievement of a critical ratio of many activators to inhibitors that triggers cell cycle entry. Here, we test the generality of this idea, by examining mRNA scaling-with-size in the yeast S. pombe and in human cells, and we will test two theories for the mechanism of differential-scaling-with-size. Finally we will ask if similar scaling occurs at the level of translation.