BIOcentre 

Lunaret Montpellier

Title :  “Post-transcriptionalcontrol of fungal cell wall synthesis by Ssd1 and co-operating RNA-bindingproteins”

Fungal cell walls are the surface where thefungus meets the world. Yet, there are major gaps in understanding offungal cell wall synthesis and its regulation, notably at thepost-transcriptional level, where the time and place of protein synthesis arecontrolled. Advances in mRNA regulation have identified several RNA-bindingproteins that regulate cell wall synthesis, however their importance in fungalcell biology remains underappreciated¹. Our recent work focuses on the RNA-binding protein Ssd1/sts5/gul-1,which is required for fungal growth and virulence, and genetically interactswith cell cycle regulators. We characterised the evolution of Ssd1’sfungal-specific RNA-binding function². We identified the RNA motif bound by Ssd1 and showed that it isenriched in the 5’UTRs of cell wall mRNAs across ascomycota³. With Atlanta Cook, we solved the structure of Ssd1³ and are investigating its mechanisms of RNA binding.

We marshal evidence across the dikaryota tobuild a model for Ssd1-mediated spatiotemporal regulation of cell wallsynthesis. Ssd1’s role as a translation repressor is demonstrated by ourfinding that Ssd1-binding motifs in reporter mRNAs repress translation in yeastSaccharomyces cerevisiae. Ssd1’s role in mRNA localisation isdemonstrated by our evidence that Ssd1-containing mRNA-protein complexesshuttle along hyphae of Aspergillus nidulans. We hypothesise that Ssd1-mediatedtranslational repression, in co-operation with other RNA-binding proteins,allows “just-in-time” local translation of cell wall components nearsites of cell wall synthesis in growing fungi. Disruption of this regulatorycircuit has profound, pleiotropic impacts on cell wall synthesis, celldivision, and stress resistance.

1.     Hall,R. A. & Wallace, E. W. J. Post-transcriptional control of fungal cell wallsynthesis. Cell Surf. 8, 100074 (2022).

2.     Ballou, E. R., Cook, A. G. & Wallace,E. W. J. Repeated Evolution of Inactive Pseudonucleases in a Fungal Branch ofthe Dis3/RNase II Family of Nucleases. Mol.Biol. Evol. 38, 1837–1846(2021).

3.         Bayne, R. A. et al.Yeast Ssd1 is a non-enzymatic member of the RNase II family with an alternativeRNA recognition site. Nucleic Acids Res.(2021) doi:10.1093/nar/gkab615.
Contact :  fabrice.caudron@igmm.cnrs.fr

– Soha Allioui, a second year PhD student in Damien Grégoire lab in IGMM. She will talk to us about « To observe is to disturb: the cost of watching tumors grow »

– Lisa Vecchio, a second year PhD student in the lab of Domenico Libri et Odil Porrua. She will talk to us about « Crac : a method for high resolution mapping of RNA-binding protein targets ».