Transcriptional and post-transcriptional gene silencing by RNA interference in Candida albicans

RNA interference (RNAi) is an epigenetic mechanism occurring in all eukaryotic cells which uses small interfering RNAs to control gene expression. siRNAs can repress gene expression transcriptionally via chromatin remodelling, or post- transcriptionally via degradation of mRNA or inhibition of translation. Candida albicians is the most common human fungal pathogen characterised by chromosomal instability, heterozygosity and diploid nature. The RNAi mechanism is well established in other systems but not in Candida where the role of two key proteins Dicer (Dcr1) and Argonaute (Ago1) is still unknown.

The aim of this project is to analyse the function of C.albicans Dcr1 and Ago1 and assess whether they have role in silencing. In other organisms, Dicer and Argonaute are not essential for cell growth and act in the same pathway. However the results of my Master project demonstrate that C. albicans Dcr1 and Ago1 act in different pathways.

Firstly, I have found that Dcr1, but not Ago1, is essential for cell growth in a temperature-dependent manner. In addition, I have demonstrated that Dcr1, but not Ago1, influences the drug resistance and hyphae formation. Finally, I have demonstrated that C. albicans RNAi silences a class of genes located at the subtelomeres and that Dcr1 but not Ago1 controls this silencing process. These results suggest that the C. albicans RNAi machinery represses gene expression independently of Ago1 via a novel uncharacterised pathway.