Given the universality of ribosomes and the almost absolute conservation of the RNase T2 family in eukaryotes, we hypothesized that the mechanism of rRNA turnover was also highly conserved in other higher organisms. To test this idea, we characterized RNase T2 proteins from several animal systems. We found evidence supporting the idea that these enzymes also carry out housekeeping functions necessary for cellular homeostasis in animals, and in collaboration with the group of A. Hurlstone (U. of Manchester, UK) we demonstrated that rRNA decay occurs in the zebrafish lysosome, and that RNASET2 is the main activity involved in this turnover. Moreover, deficiencies in this enzyme lead to lysosomal disorders that impact specifically the brain, and in humans are associated with a congenital cystic neuroencephalopathy.
We are currently using Drosophila as a model organism to study components of the RNA salvage pathway that are specific to metazoans.
Effect of starvation on the accumulation of Lysotracker-positive vesicles in larval fat body of Drosophila
Figure from Ambrosio et al (2014) PLoS ONE 9(8): e105444