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A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila

Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess the function of 447 transcription factors in the developmental growth of body wall skeletal mus...

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Autores principales: Graca, Flavia A., Sheffield, Natalie, Puppa, Melissa, Finkelstein, David, Hunt, Liam C., Demontis, Fabio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629395/
https://www.ncbi.nlm.nih.gov/pubmed/34780463
http://dx.doi.org/10.1371/journal.pgen.1009926
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author Graca, Flavia A.
Sheffield, Natalie
Puppa, Melissa
Finkelstein, David
Hunt, Liam C.
Demontis, Fabio
author_facet Graca, Flavia A.
Sheffield, Natalie
Puppa, Melissa
Finkelstein, David
Hunt, Liam C.
Demontis, Fabio
author_sort Graca, Flavia A.
collection PubMed
description Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess the function of 447 transcription factors in the developmental growth of body wall skeletal muscles in Drosophila. This screen identifies new regulators of myofiber atrophy and hypertrophy, including the transcription factor Deaf1. Deaf1 RNAi increases myofiber size whereas Deaf1 overexpression induces atrophy. Consistent with its annotation as a Gsk3 phosphorylation substrate, Deaf1 and Gsk3 induce largely overlapping transcriptional changes that are opposed by Deaf1 RNAi. The top category of Deaf1-regulated genes consists of glycolytic enzymes, which are suppressed by Deaf1 and Gsk3 but are upregulated by Deaf1 RNAi. Similar to Deaf1 and Gsk3 overexpression, RNAi for glycolytic enzymes reduces myofiber growth. Altogether, this study defines the repertoire of transcription factors that regulate developmental myofiber growth and the role of Gsk3/Deaf1/glycolysis in this process.
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spelling pubmed-86293952021-11-30 A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila Graca, Flavia A. Sheffield, Natalie Puppa, Melissa Finkelstein, David Hunt, Liam C. Demontis, Fabio PLoS Genet Research Article Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess the function of 447 transcription factors in the developmental growth of body wall skeletal muscles in Drosophila. This screen identifies new regulators of myofiber atrophy and hypertrophy, including the transcription factor Deaf1. Deaf1 RNAi increases myofiber size whereas Deaf1 overexpression induces atrophy. Consistent with its annotation as a Gsk3 phosphorylation substrate, Deaf1 and Gsk3 induce largely overlapping transcriptional changes that are opposed by Deaf1 RNAi. The top category of Deaf1-regulated genes consists of glycolytic enzymes, which are suppressed by Deaf1 and Gsk3 but are upregulated by Deaf1 RNAi. Similar to Deaf1 and Gsk3 overexpression, RNAi for glycolytic enzymes reduces myofiber growth. Altogether, this study defines the repertoire of transcription factors that regulate developmental myofiber growth and the role of Gsk3/Deaf1/glycolysis in this process. Public Library of Science 2021-11-15 /pmc/articles/PMC8629395/ /pubmed/34780463 http://dx.doi.org/10.1371/journal.pgen.1009926 Text en © 2021 Graca et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Graca, Flavia A.
Sheffield, Natalie
Puppa, Melissa
Finkelstein, David
Hunt, Liam C.
Demontis, Fabio
A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila
title A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila
title_full A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila
title_fullStr A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila
title_full_unstemmed A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila
title_short A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila
title_sort large-scale transgenic rnai screen identifies transcription factors that modulate myofiber size in drosophila
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629395/
https://www.ncbi.nlm.nih.gov/pubmed/34780463
http://dx.doi.org/10.1371/journal.pgen.1009926
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