Ricerc@Sapienza

SMN, the causative factor in SMA, is conserved from flies to humans. Recent work has shown that the Drosophila model allows identification of proteins that ameliorate the Smn loss-of-function phenotype. We found that RNAi-mediated depletion of Smn in fly neurons results in locomotion and post-eclosion defects that are ameliorated by overexpression of Tgs1, whose loss results in a phenotype similar to that elicited by Smn depletion. TGS1 (Trimethyl Guanosine Synthetase 1) adds a trimethylguanosine cap (TMG cap) to several noncoding RNAs including the snRNAs, the telomerase RNA subunit, and viral RNAs, favouring their compartmentalization in their district of function. TGS1 is enriched at the Cajal body (CB) and its catalytic activity is related to the Survival of Motor Neuron (SMN) complex, whose function is essential to prevent development of Spinal Muscular Atrophy (SMA) in humans. Our preliminary results indicate that Drosophila TGS1 (dTgs1) functions in the same pathways as its human homologue TGS1. One of these pathways involves the SMN complex and appears to be essential for proper locomotory activity. We plan to obtain novel insights into the functional relationships between TGS1 and SMN in the nervous system. We will perform genome-wide RNA seq aimed at the identification of Smn and Tgs1 RNA targets.