Proper cell‐to‐cell communication relies on signal coordination, and signal coordination relies on transcription fidelity

Abstract

Cryptic transcription is the process by which transcripts are initiated at intragenic promoters. Emerging studies indicate that transcription fidelity relies on the suppression of cryptic transcription, and this process is fine tuned in concert with signaling proteins and transcription regulators. The yeast gene STE11 is particularly important in dictating signal coordination and is well known to undergo cryptic transcription. The product of this gene, Ste11, is a protein kinase that is upstream of multiple MAP kinases, including one that promotes mating (Fus3) and another needed for adaptation to osmotic stress (Hog1). Both pathways are conserved in humans, but yeast has advantages that include unequalled genetic tractability.Our hypothesis is that cells exposed to different and simultaneous external stimuli undergo adaptations that include cryptic transcription. In particular, we propose that yeast exposed to mating pheromone and osmotic stress prioritize the osmosensing pathway. We propose further that Ste11 coordinates both mating and osmosensing pathways by 1) cryptic transcription and expression of the gene and 2) phosphorylation, activation or inactivation of the MAPKs Fus3 and Hog1. We directly measured Ste11 cryptic transcripts and protein products after stimulation of both pathways. We also monitored phosphorylation and transcriptional outputs of the MAPKs in yeast strains that increase or decrease cryptic transcription of STE11, and upon stimulation of one or both pathways.Our data indicate that cryptic Ste11 is promoted when the mating pathway is active. Furthermore, cryptic transcription elevated the osmosensing pathway and prolonged Hog1 activity. Our data indicate that cryptic transcription regulates MAPK signaling and suggest that cells use cryptic transcription as one of the strategies to coordinate responses to multiple stimuli.