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

Autoři: Paolo Maccallini aff001;  Francesca Bavasso aff001;  Livia Scatolini aff001;  Elisabetta Bucciarelli aff002;  Gemma Noviello aff001;  Veronica Lisi aff001;  Valeria Palumbo aff001;  Simone D'Angeli aff003;  Stefano Cacchione aff001;  Giovanni Cenci aff001;  Laura Ciapponi aff001;  James G. Wakefield aff005;  Maurizio Gatti aff001;  Grazia Daniela Raffa aff001
Působiště autorů: Dipartimento di Biologia e Biotecnologie “C Darwin”, Sapienza University of Rome, Rome, Italy aff001;  Istituto di Biologia e Patologia Molecolari (IBPM) del CNR, Rome, Italy aff002;  Dipartimento di Biologia Ambientale, Sapienza University of Rome, Rome, Italy aff003;  Fondazione Cenci Bolognetti, Istituto Pasteur, Rome, Italy aff004;  Biosciences/Living Systems Institute, College of Life and Environmental Sciences, University of Exeter, United Kingdom aff005
Vyšlo v časopise: Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008815
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008815


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 atrophy (SMA). Here, we analyzed the roles of the Drosophila orthologs of the human TGS1 and SMN genes. We show that the Drosophila TGS1 protein (dTgs1) physically interacts with all subunits of the Drosophila Smn complex (Smn, Gem2, Gem3, Gem4 and Gem5), and that a human TGS1 transgene rescues the mutant phenotype caused by dTgs1 loss. We demonstrate that both dTgs1 and Smn are required for viability of retinal progenitor cells and that downregulation of these genes leads to a reduced eye size. Importantly, overexpression of dTgs1 partially rescues the eye defects caused by Smn depletion, and vice versa. These results suggest that the Drosophila 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.

Klíčová slova:

Drosophila melanogaster – Eyes – Imaginal discs – Larvae – Phenotypes – RNA interference – Small nuclear RNA – Eye development


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