March 11, 2022
Meiosis in budding yeast is typically induced by starvation, with a signal roughly translated as “make spores quick because things are terrible right now.” When the outside food supply dries up, meiosis gets initiated in the nucleus of the yeast cell. If food is resupplied early enough, meiosis can pause and mitosis—a normal cell division—can be undergone instead, a process called “return to growth” (RTG). There’s a sharp point-of-no-return in mid-prometaphase, though, after which no amount of food will make cells go back to mitosis—they’ve committed to meiosis.
The components involved in this commitment to meiosis have been poorly understood. It was shown by several studies that the transcription factor Ndt80p is required at high levels to establish meiotic commitment by inducing middle meiosis genes. When levels of Ndt80p are low, in contrast, cells show a commitment defect in which they go back to mitosis even after initiating meiosis, leading to defective polyploid germ cells with multiple nuclei.
Gavade et al., in a study that just came out in Current Biology, discover six novel regulators of meiotic commitment. The authors first identified proteins whose overexpression reversed the commitment defects of a low-Ndt80 strain. The pool of potential regulators was narrowed by looking at mutants of the genes identified in the overexpression screen to see if decreased levels would cause commitment defects. They found BCY1 (involved in nutrient sensing), IME1 (a meiosis-specific kinase), CDC5 (Polo kinase, with related roles in mitosis), BMH1 and BMH2 (14-3-3- proteins involved in numerous types of signaling), and PES4 (an RNA-binding protein with an uncharacterized role in cell cycle control) to all have roles in meiotic commitment. The authors further showed that Bmh1p and Bmh2p are direct regulators of both Ndt80p and Cdc5p, the former by protein stability and the latter by protein activation.
This intriguing study is an excellent example of how complex processes—such as the effect of food on sexual reproduction—can be teased apart in yeast. A relatively simple screen was able to identify proteins not formerly known to have a role in meiotic commitment, and it will be exciting to see if these proteins have orthologs in mammals that play related roles.
Categories: Research Spotlight