气候变化领域集成服务门户(CCPortal): MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity

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DOI	10.1073/pnas.2015454118
	MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity
	Lu Y.-L.; Liu Y.; McCoy M.J.; Yoo A.S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:22
英文摘要	Neuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed by repressing antineurogenic genes. How these miRNAs function after the repression of fibroblast genes for neuronal fate remains unclear. Here, we identified targets of miR-9/9-124 as reprogramming cells activate the neuronal program and reveal the role of miR-124 that directly promotes the expression of its target genes associated with neuronal development and function. The mode of miR-124 as a positive regulator is determined by the binding of both AGO and a neuron-enriched RNA-binding protein, ELAVL3, to target transcripts. Although existing literature indicates that miRNA–ELAVL family protein interaction can result in either target gene up-regulation or down-regulation in a context-dependent manner, we specifically identified neuronal ELAVL3 as the driver for miR-124 target gene up-regulation in neurons. In primary human neurons, repressing miR-124 and ELAVL3 led to the down-regulation of genes involved in neuronal function and process outgrowth and cellular phenotypes of reduced inward currents and neurite outgrowth. Our results highlight the synergistic role between miR-124 and RNA-binding proteins to promote target gene regulation and neuronal function. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Direct reprogramming; MicroRNA target; MiR-124; Neuronal maturity; RNA-binding protein
语种	英语
scopus关键词	argonaute protein; cell protein; ELAV like protein 1; ELAV like protein 3; microRNA 124; PTBP1 protein; PTBP2 protein; unclassified drug; ELAV like protein 3; ELAVL3 protein, human; microRNA; MIRN124 microRNA, human; 3' untranslated region; adult; animal cell; Article; cell activation; cell function; cell maturation; child; controlled study; down regulation; ELAVL1 gene; ELAVL3 gene; female; gene; gene control; gene expression; gene expression regulation; gene function; genetic association; high throughput sequencing; human; human cell; male; nerve cell; nerve cell differentiation; neurite outgrowth; newborn; nonhuman; nuclear reprogramming; phenotype; preschool child; protein binding; protein expression; protein function; protein RNA binding; PTBP1 gene; PTBP2 gene; rat; upregulation; young adult; biosynthesis; gene expression regulation; genetics; metabolism; nerve cell; Adult; ELAV-Like Protein 3; Female; Gene Expression Regulation; Humans; MicroRNAs; Neurons
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251165
作者单位	Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States; Center for Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States; Program in Developmental, Regenerative and Stem Cell Biology, Washington University School of Medicine, St. Louis, MO 63110, United States; Program in Molecular Genetics and Genomics, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, United States
推荐引用方式 GB/T 7714	Lu Y.-L.,Liu Y.,McCoy M.J.,et al. MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity[J],2021,118(22).
APA	Lu Y.-L.,Liu Y.,McCoy M.J.,&Yoo A.S..(2021).MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity.Proceedings of the National Academy of Sciences of the United States of America,118(22).
MLA	Lu Y.-L.,et al."MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity".Proceedings of the National Academy of Sciences of the United States of America 118.22(2021).