Identification of a master regulator Msd1 that governs meiotic entry in a global basidiomycete pathogen
Abstract
Meiosis is a hallmark of sexual reproduction. Although the core meiotic machinery is evolutionarily conserved from unicellular yeasts to Metazoan, the key regulators responsible for initiating meiosis vary across species and remain largely unidentified in major eukaryotic lineages, including the major phylum Basidiomycota in the Kingdom Fungi. The basidiomycete fungus Cryptococcus neoformans is a critical pathogen listed by the World Health Organization that causes life-threatening meningoencephalitis worldwide. Meiosis not only indirectly facilitates cryptococcal pathogenicity through generating genetically diverse spores but also directly contributes to host adaptation and disease progression. Here, we identified a novel transcription factor Msd1 that is responsible for activating meiosis in C. neoformans . Deletion of MSD1 impaired multiple sexual development events and strikingly abolished meiosis and subsequent sporogenesis (gametogenesis). Conversely, overexpression of MSD1 alone is sufficient to drive meiosis and the formation of meiotic spores, even in the absence of the external mating-inducing cues or when the mating pathway is genetically inactivated. Mechanistically, we demonstrated that Msd1 initiates meiotic entry by targeting two interconnected pathways. First, Msd1 activates the transcription of multiple evolutionarily conserved core meiosis-specific genes such as meiotic recombinase Dmc1. Second, Msd1 activates two RNA-binding proteins, Csa1 and Csa2, which ensure spatiotemporal expression of the aforementioned meiosis-specific genes to drive meiosis and sporogenesis. Collectively, our findings demonstrate that meiosis and the sequential sexual development events are spatiotemporally orchestrated by the master regulator Msd1, and is the first reported regulator initiating meiotic entry in a basidiomycete fungus.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Fanglin Zheng
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Yanli Cao
Department of Immunology, School of Medicine, Jiangxi Medical College, Nanchang University
Huiting Chen
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Lili Yan
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Feng Lv
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Yuan Huang
Man Chen
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Lin Su
Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.
Zhuozhuo Liu
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Ye Huang
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Tuyetnhu Pham
Department of Plant Biology, University of Georgia
Xinping Xu
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
Xiaorong Lin