GSE95807
Deciphering the Regulatory Network between the SREBP pathway and Protein Secretion in Neurospora crassa
Sterol Regulatory Element Binding Proteins (SREBPs) are conserved from yeast to mammalian cells and function in regulating sterol homeostasis. In fungi, the SREBP pathway has been implicated in the adaptation to hypoxia and in virulence. In Neurospora crassa and Trichoderma reesei, the SREBP pathway also negatively regulates protein secretion under lignocellulolytic conditions. Here we utilized global transcriptional profiling combined with genetic and physiological analyses to address the regulatory link between the SREBP pathway and protein secretion in N. crassa. Our results demonstrated that the function of the SREBP pathway in ergosterol biosynthesis and adaptation to hypoxia was conserved in N. crassa. Under lignocellulolytic conditions, the SREBP pathway was highly activated, resulting in the reduced expression of lytic polysaccharide monooxygenases, which require molecular oxygen for catalytic activity. Additionally, activation of the SREBP pathway under lignocellulolytic conditions repressed a set of genes predicted to be involved in the ER stress response. Here we show that the inability of a hac-1 mutant, which bears a deletion of the major regulator of the unfolded protein response (UPR), to efficiently produce cellulases and utilize cellulose was suppressed by mutations in the SREBP pathway. The analyses presented here demonstrated new functions of SREBP pathway, including linkages to the UPR and provide new clues for genetic engineering of filamentous fungi to improve their production of extracellular proteins. Overall design: Examination of mRNA levels of four strains WT, ?sah-2, Mclr-2 and Mclr-2?sah-2 strains grown in sucrose minimal media for 24 hours after a shift from 16 hours in VMM by RNA -Seq. Each sample was set as three biological replicates.