Nutrient Control of Yeast Gametogenesis Is Mediated by TORC1, PKA and Energy Availability

Abstract

Cell fate choices are tightly controlled by the interplay between intrinsic and extrinsic signals, and gene regulatory networks. In Saccharomyces cerevisiae, the decision to enter into gametogenesis or sporulation is dictated by mating type and nutrient availability. These signals regulate the expression of the master regulator of gametogenesis, IME1. Here we describe how nutrients control IME1 expression. We find that protein kinase A (PKA) and target of rapamycin complex I (TORC1) signalling mediate nutrient regulation of IME1 expression. Inhibiting both pathways is sufficient to induce IME1 expression and complete sporulation in nutrient-rich conditions. Our ability to induce sporulation under nutrient rich conditions allowed us to show that respiration and fermentation are interchangeable energy sources for IME1 transcription. Furthermore, we find that TORC1 can both promote and inhibit gametogenesis. Down-regulation of TORC1 is required to activate IME1. However, complete inactivation of TORC1 inhibits IME1 induction, indicating that an intermediate level of TORC1 signalling is required for entry into sporulation. Finally, we show that the transcriptional repressor Tup1 binds and represses the IME1 promoter when nutrients are ample, but is released from the IME1 promoter when both PKA and TORC1 are inhibited. Collectively our data demonstrate that nutrient control of entry into sporulation is mediated by a combination of energy availability, TORC1 and PKA activities that converge on the IME1 promoter.

Temporal Expression of a Master Regulator Drives Synchronous Sporulation in Budding Yeast

“…Inducing IME1 too late could affect sporulation, because cells have been starved for prolonged times, whereas inducing IME1 too early does not result in optimal sporulation because cells are not ready. In line with this hypothesis, in a recent report we showed that a certain level of nutrient-sensing target of rapamycin complex (TORC1) activity is needed for sporulation (Weidberg et al 2016). Too much or too little TORC1 affects sporulation negatively.…”

Transcription of the mating-type-regulated lncRNA IRT1 is governed by TORC1 and PKA

“…The tup1 Δ strain was generated using one-step deletion protocol as described by Longtine et al (1998). The tpk1as and Rme1-V5 alleles were described previously (van Werven et al 2012; Weidberg et al 2016). The genotypes of the strains used for this study are described in Table 1.…”

“…These signals integrate at the promoter of the master regulator for entry into sporulation, called IME1 (Kassir et al 1988; Nachman et al 2007). When nutrients are ample, IME1 is repressed because the two major nutrient sensing signalling pathways, protein kinase A and target of rapamycin complex I (TORC1), are active (Weidberg et al 2016). In the absence of nitrogen and glucose compounds in the growth medium, TORC1 and PKA activities are repressed and IME1 is strongly induced.…”

“…In budding yeast, the decision to enter gametogenesis or sporulation is dictated by nutrient availability and mating type. Recently, we showed that in diploid cells harbouring opposite mating types ( MAT a and MAT α), the protein kinase A (PKA) and target of rapamycin complex I (TORC1) signalling pathways integrate at the promoter of the master regulatory transcription factor IME1 to control sporulation via nutrient availability (Weidberg, et al 2016). In cells with a single mating type ( MAT a or MAT α), however, IME1 is repressed by transcription through the IME1 promoter of a long non-coding RNA called IRT1 , which prevents this cell type from undergoing sporulation.…”

Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation

“…TorC1 also specifically represses sporulation by preventing nuclear localization/activation of Ime1p 172. Interestingly, a low level of TorC1 is required for IME1 expression; thus sporulation only initiates with moderate TorC1 activity 230. In addition, once cells become quiescent, activation of TorC1 diminishes their viability (i.e.…”