Intimate functional interactions between   < i > TGS1 < /i > and the < i > Smn < /i >  complex revealed by an analysis of the < i > Drosophila < /i > eye development

by Paolo Maccallini, Francesca Bavasso, Livia Scatolini, Elisabetta Bucciarelli, Gemma Noviello, Veronica Lisi, Valeria Palumbo, Simone D'Angeli, Stefano Cacchione, Giovanni Cenci, Laura Ciapponi, James G. Wakefield, Maurizio Gatti, Grazia Daniela Raffa Trimethylguanosine synthase 1 (TGS1) is a conserved enzyme that mediates formation of the trimethylguanosine cap on several RNAs, including snRNAs and telomerase RNA. Previous studies have shown that TGS1 binds the Survival Motor Neuron (SMN) protein, whose deficiency causes spinal muscular atroph y (SMA). Here, we analyzed the roles of theDrosophila orthologs of the humanTGS1 andSMN genes. We show that theDrosophila TGS1 protein (dTgs1) physically interacts with all subunits of theDrosophila Smn complex (Smn, Gem2, Gem3, Gem4 and Gem5), and that a humanTGS1 transgene rescues the mutant phenotype caused bydTgs1 loss. We demonstrate that bothdTgs1 andSmn are required for viability of retinal progenitor cells and that downregulation of these genes leads to a reduced eye size. Importantly, overexpression ofdTgs1 partially rescues the eye defects caused by Smn depletion, and vice versa. These results suggest that theDrosophila eye model can be exploited for screens aimed at the identification of genes and drugs that modify the phenotypes elicited by Tgs1 and Smn deficiency. These modifiers could help to understand the molecular mechanisms underlying SMA pathogenesis and devise new therapies for this genetic disease.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research