Poster number 123 submitted by Melissa Tosiano
RNP granule condensation: a potential mechanism for post-transcriptional regulation of the yeast-to-hyphal transition in Candida albicans
Melissa A. Tosiano (Biological Sciences, Carnegie Mellon University ), Fred Lanni (Biological Sciences, Carnegie Mellon University ), Gemma E. May (Biological Sciences, Carnegie Mellon University ), C. Joel McManus (Biological Sciences, Carnegie Mellon University )
Localization of mRNA to ribonucleoprotein granules (RNPs) such as P-bodies (PBs) and stress granules (SGs) is an integral part of the eukaryotic stress response. RNPs have been extensively studied in S. cerevisiae where they are important for translational repression as well as reprogramming the transcriptome. In diverse yeast species, DEAD-box helicase Ded1p acts as a translation initiation factor during active growth1. Conversely, heat shock induces Ded1p condensation, selectively repressing housekeeping mRNAs in SGs1. However, the extent to which these functions of RNPs and Ded1p are conserved in other fungi remains opaque.
The human opportunistic fungal pathogen Candida albicans responds to heat stress and starvation by forming filamentous hyphae, which are strongly linked to virulence2. Prior work demonstrated that C. albicans forms PBs and SGs in response to various stressors3-4, and the PB component Edc3p is required for typical filamentation4. However, the molecular mechanisms by which PBs promote filamentation have not been determined. Additionally, the importance of SGs and Ded1p in this phenotypic shift has not been investigated.
To examine RNP formation during C. albicans filamentation, we fluorescently tagged canonical SG (PAB1) and PB (EDC3) markers as well as DED1 in the genome and examined their condensation. We found that PBs, SGs, and Ded1p condense in response to acute heat shock. Interestingly, SGs and Ded1p fail to form condensates during physiologically relevant filamentation conditions, while abundant PBs condense along the developing germ tube. In the future we will examine the transcriptome, morphology, and virulence of an edc3/edc3 strain to elucidate the contribution of PBs to C. albicans filamentation.
1. Iserman, C. et al. Condensation of Ded1p Promotes a Translational Switch from Housekeeping to Stress Protein Production. Cell 181, 818-831.e19 (2020).
2.Thompson, D. S., et al. Coevolution of morphology and virulence in Candida species. Eukaryot. Cell 10, 1173–1182 2011.
3. O’Meara, T. R. et al. Global proteomic analyses define an environmentally contingent Hsp90 interactome and reveal chaperone-dependent regulation of stress granule proteins and the R2TP complex in a fungal pathogen. PLoS Biology 17, 1-38 (2019).
4. Jung, J. H. & Kim, J. Accumulation of P-bodies in Candida albicans under different stress and filamentous growth conditions. Fungal Genet. Biol. 48, 1116–1123 (2011).
Keywords: P-Bodies, C albicans, post-transcriptional regulation