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

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...

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Autores principales: Maccallini, Paolo, Bavasso, Francesca, Scatolini, Livia, Bucciarelli, Elisabetta, Noviello, Gemma, Lisi, Veronica, Palumbo, Valeria, D'Angeli, Simone, Cacchione, Stefano, Cenci, Giovanni, Ciapponi, Laura, Wakefield, James G., Gatti, Maurizio, Raffa, Grazia Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289441/
https://www.ncbi.nlm.nih.gov/pubmed/32453722
http://dx.doi.org/10.1371/journal.pgen.1008815
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author Maccallini, Paolo
Bavasso, Francesca
Scatolini, Livia
Bucciarelli, Elisabetta
Noviello, Gemma
Lisi, Veronica
Palumbo, Valeria
D'Angeli, Simone
Cacchione, Stefano
Cenci, Giovanni
Ciapponi, Laura
Wakefield, James G.
Gatti, Maurizio
Raffa, Grazia Daniela
author_facet Maccallini, Paolo
Bavasso, Francesca
Scatolini, Livia
Bucciarelli, Elisabetta
Noviello, Gemma
Lisi, Veronica
Palumbo, Valeria
D'Angeli, Simone
Cacchione, Stefano
Cenci, Giovanni
Ciapponi, Laura
Wakefield, James G.
Gatti, Maurizio
Raffa, Grazia Daniela
author_sort Maccallini, Paolo
collection PubMed
description 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.
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spelling pubmed-72894412020-06-18 Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development Maccallini, Paolo Bavasso, Francesca Scatolini, Livia Bucciarelli, Elisabetta Noviello, Gemma Lisi, Veronica Palumbo, Valeria D'Angeli, Simone Cacchione, Stefano Cenci, Giovanni Ciapponi, Laura Wakefield, James G. Gatti, Maurizio Raffa, Grazia Daniela PLoS Genet Research Article 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. Public Library of Science 2020-05-26 /pmc/articles/PMC7289441/ /pubmed/32453722 http://dx.doi.org/10.1371/journal.pgen.1008815 Text en © 2020 Maccallini et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Maccallini, Paolo
Bavasso, Francesca
Scatolini, Livia
Bucciarelli, Elisabetta
Noviello, Gemma
Lisi, Veronica
Palumbo, Valeria
D'Angeli, Simone
Cacchione, Stefano
Cenci, Giovanni
Ciapponi, Laura
Wakefield, James G.
Gatti, Maurizio
Raffa, Grazia Daniela
Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development
title Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development
title_full Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development
title_fullStr Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development
title_full_unstemmed Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development
title_short Intimate functional interactions between TGS1 and the Smn complex revealed by an analysis of the Drosophila eye development
title_sort intimate functional interactions between tgs1 and the smn complex revealed by an analysis of the drosophila eye development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289441/
https://www.ncbi.nlm.nih.gov/pubmed/32453722
http://dx.doi.org/10.1371/journal.pgen.1008815
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