Poster abstracts
Poster number 66 submitted by Lucia Johnson
Transcriptional and Translational responses to stress in Cryptococcus neoformans
Lucia Johnson (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA), Corey Knowles (Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA), Gemma May (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA), Alexandra Benedetto (Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA), C. Joel McManus (Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA), John Panepinto (Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA)
Abstract:
Cryptococcus neoformans is an important fungal pathogen that causes 180,000 deaths worldwide per year (1). In order to cause disease and survive the host immune response, this microbe adapts to numerous stresses, including oxidative stress and increased body temperature. While the transcriptional responses to these stressors have been well studied, much less is known about how mRNA translational control contributes to adaptation to these stressors. This could be particularly important, as prior work has shown that post-transcriptional regulation plays a vital role in fungal stress responses. Here, we used Ribosome profiling and RNA-seq to compare and contrast the translational and transcriptional responses to heat shock and oxidative stress in C. neoformans. While most of the expression response involves changes to mRNA abundance, we found widespread changes in translation regulation in response to stress, including important pathways involved in metabolism and capsid/cell wall synthesis. We also identified hundreds of uORFs in C. neoformans and found both increases and decreases in uORF usage that have a major effect on translation efficiency in response to stress. Together, these results reveal intricate regulation of mRNA translation in response to stresses in this opportunistic fungal pathogen that are influenced by mRNA abundance, alternative mRNA splicing and differential utilization of uORFs.
References:
1. Rajasingham et al., The Lancet. Infectious diseases PMID: 36049486
Keywords: alternative splicing, translation