| Regulating cellular and chemical development requires an intricate network of interacting genetic elements. In Aspergillus, the ascomycetous fungus, various upstream regulators have been found to play key roles in regulating development and metabolism. Through a gain-offunction screen of sporulation repressors, we were able to identify the osaA gene predicted to encode a WOPR domain protein in Aspergillus nidulans. This dissertation describes the role of WOPR proteins in the genus Aspergillus. The WOPR domain protein family is fungal-specific and represents a novel class of DNA-binding proteins. In A. nidulans, osaA multi-copy disrupted the fungus normal lifecycle and led to enhanced proliferation of vegetative growth. Loss of osaA, on the other hand, resulted in stimulated state of sexual development, accompanied by reduced asexual development (conidiation), thus named as osaA ( Orchestrator of Sex and Asex). Further genetic studies showed that OsaA balances development mainly by repressing sexual fruiting downstream of the velvet regulator VeA. The absence of osaA is sufficient to suppress the veA1 allele leading to sporulation levels comparable to veA+ wild type (WT). Genome-wide transcriptomic analyses conducted on WT, veA1 and DeltaosaA veA1 strains further confirmed the competence of DeltaosaA in suppressing veA1 mutation and bringing the genome-wide expression closer to veA+ WT. The transcriptomic analyses also showed that OsaA and VeA are not exclusive to development and their influence covers different aspects of fungal biology; e.g. metabolism and cell wall synthesis. Deletion mutants of OsaA orthologs in A. fumigatus and A. flavus (AfuWprA and AflWprA, respectively) show aberrations in development and mycotoxin biogenesis. A. flavus wprA was able to complement the osaA null phenotype in A. nidulans, suggesting a conserved role of this group of WOPR domain proteins. In summary, WOPR proteins are key regulatory factors that participate in controlling morphological and chemical developments in Aspergillus species. |
