title: Opposing PKA and Hog1 signals control the post-transcriptional response to glucose availability in Cryptococcus neoformans.
abstract: The pathogenic fungus Cryptococcus neoformans must adapt to glucose-limited conditions in the lung and glucose replete conditions upon dissemination to the brain. We report that glucose controls ribosome biogenesis and translation by modulating mRNA decay through a balance of PKA and Hog1 signalling. Glucose signalling through PKA stabilized ribosomal protein (RP) mRNAs whereas glucose starvation destabilized RP transcripts through Hog1. Glucose starvation-induced oxidative stress response genes, and treatment of glucose-fed cells with reactive oxygen species (ROS) generating compounds repressed RP transcripts, both of which were dependent on Hog1. Stabilization of RP transcripts led to retention of polysomes in a hog1Δ mutant, whereas stabilization of RP transcripts by cyclic AMP did not affect translation repression, suggesting that Hog1 alone signals translation repression. In sum, this work describes a novel antagonism between PKA and Hog1 controlling ribosome biogenesis via mRNA stability in response to glucose availability in this important human pathogen.
authors.affiliation: Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
authors.forename: Dithi
authors.initials: D
authors.lastname: Banerjee
authors.affiliation: Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
authors.forename: Amanda L M
authors.initials: AL
authors.lastname: Bloom
authors.affiliation: Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY, 14214, USA. jcp25@buffalo.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Panepinto
mesh_terms: D003453:Cryptococcosis / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose