The WOR1 5 untranslated region regulates white-opaque switching in Candida albicans by reducing translational efficiency

The human fungal pathogen Candida albicans undergoes white-opaque phenotypic switching, which enhances its adaptation to host niches. Switching is controlled by a transcriptional regulatory network of interlocking feedback loops acting on the transcription of WOR1, the master regulator of white-opaque switching, but regulation of the network on the translational level is not yet explored. Here, we show that the long 5 untranslated region of WOR1 regulates the white-opaque phenotype. Deletion of the WOR1 5 UTR promotes white-to-opaque switching and stabilizes the opaque state. The WOR1 5 UTR reduces translational efficiency and the association of the transcript with polysomes. Reduced polysome association was observed for additional key regulators of cell fate and morphology with long 5 UTR as well. Overall, we find a novel regulatory step of white-opaque switching at the translational level. This translational regulation is implicated for many key regulators of cell fate and morphology in C.albicans.