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

Abstract

Cell fate decisions are controlled by multiple cell-intrinsic and -extrinsic factors. 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 (MATa and MATα), 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 (MATa or MATα), 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. Here, we investigated the role of nutrient signalling in mating-type control of IME1. We find that expression of IRT1, like IME1 itself, depends on nutrient availability and the activities of PKA and TORC1. IRT1 transcription is repressed when nutrients are ample and TORC1 and PKA are active. In contrast, inhibition of PKA and TORC1 is sufficient to recruit Rme1 to the IRT1 promoter and induce IRT1-mediated repression of IME1. Finally, we provide evidence that IRT1 and IME1 are co-repressed by the Tup1–Cyc8 complex when nutrients are ample. Thus, in cells with a single mating-type nutrient availability regulates mating-type repression of IME1 and sporulation. Our results indicate that there is a hierarchy between nutrient and mating-type signals in controlling the decision to enter sporulation.

A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast

“…The starvation signal, which is the primary signal for activation of IRT1 and IME1 transcription, was considered to be either off (0) or on (1) (Fig. 7b ) 19 , 30 . We note that this simple model is sufficient to reflect the experimental data.…”

A current view on long noncoding RNAs in yeast and filamentous fungi

“…Under nutrient-rich conditions, PKA (protein kinase A) and TORC1 (target of rapamycin complex I) are produced in both haploid and diploid cells. Those factors are required for binding of the Tup1–Cyc8 complex to the IME1 locus and hence direct inhibition of both IME1 and IRT1 when nutrients are available (Moretto and van Werven 2017). Synergistically, the mechanisms based on regulation by PKA/TORC and Rme1 allow tightly control of entry into meiosis only upon nutrient starvation and in heterozygous diploid S. cerevisiae cells exclusively.…”

Crossbreeding of Yeasts Domesticated for Fermentation: Infertility Challenges

“…MAT mating type locus; a or α allele [7,8] STE2 seven transmembrane receptor for α-factor pheromone [18] STE3 seven transmembrane receptor for a-factor pheromone [18] MFA1 mating pheromone a-factor [18] MFα1 mating pheromone α-factor [18] GPA1 GTP-binding α subunit of heterotrimeric G-protein [18,19] STE4 β subunit of heterotrimeric G-protein [18,19] STE18 γ subunit of heterotrimeric G-protein [18,19] IME1 master regulator of meiosis [20] RME1 zinc finger protein involved in control of meiosis [20] IRT1 long noncoding RNA located in the IME1 promoter [21] HMRa * silenced copy of a sequence [22] HMLα silenced copy of α sequence [22] HO site-specific endonuclease for the MAT locus [18] ASH1 zinc-finger inhibitor of HO transcription [23] SHE1 type V myosin motor involved in actin-based transport [24] SHE2 RNA-binding protein that binds specific mRNAs [24] SHE3 protein adaptor between She1 and the She2-mRNA complex [24] MSN2 stress responsive transcriptional activator [25,26] MSN4 stress responsive transcriptional activator [25,26] RIM15 protein kinase involved in cell proliferation [27] IME2 serine/threonine protein kinase involved in activation of meiosis [28,29] GIS1 histone demethylase and transcription factor [30] SPO11 meiosis-specific protein that initiates meiotic recombination [31]…”