GSE184618
The Rim15p homolog RimO mediates starvation response and is required for secondary metabolite production in Aspergillus nidulans
Depending on the prevailing environmental, developmental and nutritional conditions Aspergillus nidulans produces different combinations of secondary metabolites (SMs). To activate the biosynthetic gene cluster (BGC) for a given SM global, chromatin-based de-repression must be integrated with pathway-specific induction signals. Here we describe a new global regulator affecting the set of starvation-induced SMs. We found a hitherto uncharacterized putative PAS-domain containing kinase to be upregulated in SM-producing cultures. The predicted protein is highly similar to yeast Rim15 which transmits nutritional and stress signals to downstream effectors involved in chromatin regulation, stress and starvation response. The putative kinase – termed RimO – is required for the transcription of a number of starvation-induced SMs including sterigmatocystin (ST). RimO regulates the pathway-specific transcription factor AflR both at the transcriptional and post-translational level. In the absence of RimO aflR is barely transcribed under SM conditions and the protein is not retained in the nucleus. Genome-wide transcriptional profiling showed that cells lacking rimO fail to correctly respond to carbon and nitrogen starvation and continue to transcribe genes of the basic metabolism to a high level. Conversely, overexpression of the kinase made cells largely insensitive to glucose repression and led to overproduction of several secondary metabolites. We propose a model that positions RimO downstream of PKA being necessary to transmit the starvation signal to downstream targets, including chromatin and transcriptional regulators of SM gene clusters. Additionally, it may also regulate signaling modules required for recognizing the starvation response. Overall design: 12 Samples of A. nidulans, 3 Types: wild type, rimO deletion and rimO over expression , 2 time points of harvest (17h and 48h or 54h post inocculation), all samples are replicated