title: Thyroid hormone regulates muscle fiber type conversion via miR-133a1.
abstract: It is known that thyroid hormone (TH) is a major determinant of muscle fiber composition, but the molecular mechanism by which it does so remains unclear. Here, we demonstrated that miR-133a1 is a direct target gene of TH in muscle. Intriguingly, miR-133a, which is enriched in fast-twitch muscle, regulates slow-to-fast muscle fiber type conversion by targeting TEA domain family member 1 (TEAD1), a key regulator of slow muscle gene expression. Inhibition of miR-133a in vivo abrogated TH action on muscle fiber type conversion. Moreover, TEAD1 overexpression antagonized the effect of miR-133a as well as TH on muscle fiber type switch. Additionally, we demonstrate that TH negatively regulates the transcription of myosin heavy chain I indirectly via miR-133a/TEAD1. Collectively, we propose that TH inhibits the slow muscle phenotype through a novel epigenetic mechanism involving repression of TEAD1 expression via targeting by miR-133a1. This identification of a TH-regulated microRNA therefore sheds new light on how TH achieves its diverse biological activities.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neuromuscular Disease, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, and Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Lu
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Nutrition, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, and Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Mo-Fang
authors.initials: MF
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Neuromuscular Disease, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Xihua
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; and Center for RNA Research, State Key Laboratory of Molecular Biology; University of Chinese Academy of Sciences, Shanghai 200031, China Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, and Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China yinghao@sibs.ac.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D051381:Rats; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors; C519276:myosin heavy chain-1, mouse; D014284:Triiodothyronine; D018995:Myosin Heavy Chains