Rlm1 mediates positive autoregulatory transcriptional feedback that is essential for Slt2-dependent gene expression.

Activation of the yeast cell wall integrity (CWI) pathway induces an adaptive transcriptional programme that is largely dependent on the transcription factor Rlm1 and the mitogen-activated protein kinase (MAPK) Slt2. Upon cell wall stress, the transcription factor Rlm1 is recruited to the promoters of RLM1 and SLT2, and exerts positive-feedback mechanisms on the expression of both genes. Activation of the MAPK Slt2 by cell wall stress is not impaired in strains with individual blockade of any of the two feedback pathways. Abrogation of the autoregulatory feedback mechanism on RLM1 severely affects the transcriptional response elicited by activation of the CWI pathway. In contrast, a positive trans-acting feedback mechanism exerted by Rlm1 on SLT2 also regulates CWI output responses but to a lesser extent. Therefore, a complete CWI transcriptional response requires not only phosphorylation of Rlm1 by Slt2 but also concurrent SLT2- and RLM1-mediated positive-feedback mechanisms; sustained patterns of gene expression are mainly achieved by positive autoregulatory circuits based on the transcriptional activation of Rlm1.