title: PyrG is required for maintaining stable cellular uracil level and normal sporulation pattern under excess uracil stress in Aspergillus nidulans.
abstract: Tight control of the intracellular uracil level is believed to be important to reduce the occurrence of uracil incorporation into DNA. The pyrG gene of Aspergillus nidulans encodes orotidine 5'-phosphate decarboxylase, which catalyzes the conversion of orotidine monophosphate (OMP) to uridine monophosphate (UMP). In this study, we found that pyrG is critical for maintaining uracil at a low concentration in A. nidulans cells in the presence of exogenous uracil. Excess uracil and its derivatives had a stronger inhibitory effect on the growth of the pyrG89 mutant with defective OMP decarboxylase activity than on the growth of wild type, and induced sexual development in the pyrG89 mutant but not in wild type. Analysis of transcriptomic responses to excess uracil by digital gene expression profiling (DGE) revealed that genes related to sexual development were transcriptionally activated in the pyrG89 mutant but not in wild type. Quantitative analysis by HPLC showed that the cellular uracil level was 6.5 times higher in the pyrG89 mutant than in wild type in the presence of exogenous uracil. This study not only provides new information on uracil recycling and adaptation to excess uracil but also reveals the potential effects of OMP decarboxylase on fungal growth and development.
authors: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
authors: Xianyun
authors: X
authors: Sun
authors: Jufen
authors: J
authors: Zhu
authors: Li
authors: L
authors: Bao
authors: Chengcheng
authors: C
authors: Hu
authors: Cheng
authors: C
authors: Jin
authors: Steven D
authors: SD
authors: Harris
authors: Hongwei
authors: H
authors: Liu
authors: Shaojie
authors: S
authors: Li
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014498:Uracil / Q000378:metabolism* / Q000494:pharmacology; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; C005417:orotidylic acid; D014498:Uracil; D014542:Uridine Monophosphate; D009964:Orotidine-5'-Phosphate Decarboxylase