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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7289441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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