Talk abstracts
Talk on Friday 01:45-02:00pm submitted by Corey Knowles
Effectors of stress-responsive translational repression in C. neoformans
Corey M. Knowles (Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA), John C. Panepinto (Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA)
Abstract:
Cryptococcus neoformans is a ubiquitous environmental fungus and opportunistic human pathogen, primarily impacting immunocompromised hosts such as those living with HIV/AIDS. One of C. neoformans key virulence traits is its ability to undergo the rapid transition from surviving in its environmental niche, to surviving the harsh environment inside of the human lung. Here, it is subject to the sudden temperature shift to the human core temperature of 37°C, and oxidative stress from resident lung macrophages, among other stressors. In a wild type (WT) strain, exposure to these stressors results in ribosome collision accompanied by a repression in translation, and rapid decay of abundant homeostatic mRNAs, many of which code for ribosomal proteins. This response results in a translatome reprogramming, that promotes translation of mRNAs encoding stress response effectors. Our previous work has identified Ccr4-dependent mRNA decay to be a requirement for translatome reprogramming in response to stress in C. neoformans, and as a result, a ccr4Δ mutant is broadly stress sensitive. This observation has led us to investigate additional paths to translational repression, testing the hypothesis that stress responsive translatome reprogramming will require regulation of translation at the ribosome. Gcn2, the sole kinase of eIF2α in C. neoformans, is required for translational repression and subsequent RP mRNA decay during oxidative stress from H2O2, but is completely dispensable for adaptation to host temperature stress of 37°C. Additionally, a gcn2Δ mutant is sensitive to oxidative stress, and exhibits persistent disome accumulation. These results point to deadenylation-dependent decay as a convergence point for translatome reprogramming in C. neoformans, and suggest that individual stressors and their magnitude contribute to the translational response to stress in this important pathogen through different ribosome associated pathways. Future work will determine which components of the ribosome quality control machinery are necessary for recognizing and resolving these changes in translation in response to environmental stressors relevant to host adaptation.
Keywords: translation regulation, ribosome collision, cellular stress