Poster abstracts

Poster number 101 submitted by Melissa Tosiano

Alternative transcription start sites (aTSS): a mechanism for post-transcriptional regulation of C. albicans filamentation

Melissa A. Tosiano (Biological Sciences, Carnegie Mellon University ), Gemma E. May (Biological Sciences, Carnegie Mellon University ), Derek Wang (Biological Sciences, Carnegie Mellon University ), C. Joel McManus (Biological Sciences, Carnegie Mellon University )

Abstract:
While Candida albicans lives as a commensal organism in healthy humans, it can cause candidiasis in immunocompromised individuals. Its ability to detect and respond to stressors in diverse physiological microenvironments is required for pathogenicity1. In response to stress, C. albicans undergoes filamentation - shifting from yeast to virulent hyphae2. Post-transcriptional regulation contributes to eukaryotic stress responses and may play a role in C. albicans filamentation. Indeed, the TLs of UME6 and EFG1, two C. albicans filamentation inducing transcription factors, possess long complex 5’ TLs hypothesized to modulate translation3,4. Alternative transcription start sites (aTSSs) create transcript leaders with substantially different translation efficiencies in other fungi5 and can lead to N-terminally truncated proteins and / or decreased expression through nonsense-mediated mRNA decay (NMD). This suggests a role for aTSSs during C. albicans filamentation. Using public C. albicans TL sequencing data, we evaluated the locations of m7G capped transcription start site (TSS) peaks. We found many ORFs possess at least one alternative TSS, a fraction of which had an aTSS within the CDS. Additionally, we identified 575 ORFs with long TLs likely to contain cis-regulatory elements. Using 5’ end sequencing we generated TL maps from C. albicans before and 90 minutes after exposure to filament inducing stress. In our future work, we will quantify TE of differential TLs transcribed in the yeast and hyphal phenotypes.

References:
1. Brown, A. J. P. et al. Stress adaptation in a pathogenic fungus. J. Exp. Biol. 217, 144–155 2014.
2. Thompson, D. S., et al. Coevolution of morphology and virulence in Candida species. Eukaryot. Cell 10, 1173–1182 2011.
3. Desai, P. R. et al. The 5’ Untranslated Region of EFG1 Transcript Promotes Its Translation To Regulate Hyphal Morphogenesis in C. albicans. mSphere. 3, 1–15 2018.
4. Childers, D. S., et al. A 5’ UTR-mediated translational efficiency mechanism inhibits the C. albicans morphological transition. Mol. Microbiol. 92, 570–585 2014.
5. Arribere, J. A. & Gilbert, W. V. Roles for TLs in translation and mRNA decay revealed by transcript leader sequencing. Gen. Res. 23, 977–987 2013.

Keywords: C albicans, aTSS, post-transcriptional regulation