Initiation of the yeast G0 program requires Igo1 and Igo2, which antagonize activation of decapping of specific nutrient-regulated mRNAs.

Growth factors and essential nutrients are key controllers of eukaryotic cell proliferation. In their absence, cells may enter into a quiescent (G0) state. In yeast, nitrogen and/or carbon limitation causes downregulation of the conserved TORC1 and PKA signaling pathways and consequently activation of Rim15, a member of the PAS protein kinase family. Rim15 orchestrates the initiation of the G0 program in part by coordinating transcription of Msn2/4- and/or Gis1-dependent genes with posttranscriptional protection of the corresponding mRNAs via direct phosphorylation of Igo1/2. Here, we show that several factors including Ccr4, the Lsm-Pat1 complex, and Dhh1, which are implicated in mRNA decapping activation, participate in the decay of specific mRNAs during initiation of the G0 program when Igo1/2 are absent. Accordingly, Igo1/2 likely play a key role in preventing the decapping and subsequent 5'-3' degradation of a set of nutrient-regulated mRNAs that are critical for cell differentiation and chronological life span.