Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex

Production of secondary metabolites is controlled by a complicated regulatory network in eukaryotic cells. Several layers of regulators are involved in this process, ranging from pathway-specific regulation, to epigenetic control, to global regulation. Unprecedentedly, we have discovered that interaction of an RNA-binding protein CsdA with a regulator RsdA coordinates fungal secondary metabolism. Employing a genetic deletion approach and transcriptome analysis as well as metabolomics analysis, we revealed that CsdA and RsdA synergistically regulate fungal secondary metabolism comprehensively. Mechanistically, comprehensive genetic and biochemical studies proved that RsdA and CsdA co-localize in the nucleus and physically interact to achieve their function. In particular, we have demonstrated that CsdA mediates rsdA expression by binding specific motif “GUCGGUAU” of its pre-mRNA at a post-transcriptional level. We thus uncover a general mechanism in which RNA-binding protein physically interacts with, and controls the expression level of, the RsdA to coordinate fungal secondary metabolism. Overall design: Mycelial RNA from Pestalotiopsis fici wild type and mutants for 5 days.