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大规模转基因 RNAi 筛选鉴定出调节果蝇肌纤维大小的转录因子。

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

机构信息

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.

出版信息

PLoS Genet. 2021 Nov 15;17(11):e1009926. doi: 10.1371/journal.pgen.1009926. eCollection 2021 Nov.

DOI:10.1371/journal.pgen.1009926
PMID:34780463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8629395/
Abstract

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.

摘要

肌纤维萎缩发生在衰老和许多疾病中，但潜在机制尚不完全清楚。在这里，我们使用了超过 1100 种肌肉靶向 RNAi 干预措施，全面评估了 447 种转录因子在果蝇体壁骨骼肌发育生长中的作用。该筛选鉴定了肌纤维萎缩和肥大的新调节因子，包括转录因子 Deaf1。Deaf1 RNAi 增加肌纤维大小，而过表达 Deaf1 则诱导萎缩。与其作为 Gsk3 磷酸化底物的注释一致，Deaf1 和 Gsk3 诱导的转录变化基本重叠，而 Deaf1 RNAi 则相反。Deaf1 调节的基因的主要类别是糖酵解酶，这些酶被 Deaf1 和 Gsk3 抑制，但被 Deaf1 RNAi 上调。与 Deaf1 和 Gsk3 过表达相似，糖酵解酶的 RNAi 会减少肌纤维生长。总的来说，这项研究定义了调节发育性肌纤维生长的转录因子组合，以及 Gsk3/Deaf1/糖酵解在这一过程中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/d97e6b49d2f6/pgen.1009926.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/cdad9f1da5e4/pgen.1009926.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/79d51a7f5a1b/pgen.1009926.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/99834c672887/pgen.1009926.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/2998f16fd469/pgen.1009926.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/d97e6b49d2f6/pgen.1009926.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/cdad9f1da5e4/pgen.1009926.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/79d51a7f5a1b/pgen.1009926.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/99834c672887/pgen.1009926.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/2998f16fd469/pgen.1009926.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb58/8629395/d97e6b49d2f6/pgen.1009926.g005.jpg

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