Feed-forward regulation of a cell fate determinant by an RNA-binding protein generates asymmetry in yeast

Saccharomyces cerevisiae can divide asymmetrically so that the mother and daughter cells have different fates. We show that the RNA-binding protein Khd1 regulates asymmetric expression of FLO11 to determine daughter cell fate during filamentous growth. Khd1 represses transcription of FLO11 indirectly through its regulation of ASH1 mRNA. Khd1 also represses FLO11 through a post-transcriptional mechanism independent of ASH1. Cross-linking immunoprecipitation (CLIP) coupled with high-throughput sequencing shows that Khd1 directly binds repetitive sequences in FLO11 mRNA. Khd1 inhibits translation through this interaction, establishing feed-forward repression of FLO11. This regulation enables changes in FLO11 expression between mother and daughter cells, which establishes the asymmetry required for the developmental transition between yeast form and filamentous growth.