title: Translational suppression of atrophic regulators by microRNA-23a integrates resistance to skeletal muscle atrophy.
abstract: Muscle atrophy is caused by accelerated protein degradation and occurs in many pathological states. Two muscle-specific ubiquitin ligases, MAFbx/atrogin-1 and muscle RING-finger 1 (MuRF1), are prominently induced during muscle atrophy and mediate atrophy-associated protein degradation. Blocking the expression of these two ubiquitin ligases provides protection against muscle atrophy. Here we report that miR-23a suppresses the translation of both MAFbx/atrogin-1 and MuRF1 in a 3'-UTR-dependent manner. Ectopic expression of miR-23a is sufficient to protect muscles from atrophy in vitro and in vivo. Furthermore, miR-23a transgenic mice showed resistance against glucocorticoid-induced skeletal muscle atrophy. These data suggest that suppression of multiple regulators by a single miRNA can have significant consequences in adult tissues.
authors.affiliation: Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Wada
authors.affiliation: Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8562, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Institute for Biomedical Engineering Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku, Tokyo 162-0041, Japan; Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Okutsu
authors.affiliation: Department of Regenerative Biology and Medicine, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyaki
authors.affiliation: Institute for Biomedical Engineering Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku, Tokyo 162-0041, Japan; Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Venetian Institute of Molecular Medicine, 35129 Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Schiaffino
authors.affiliation: Department of Regenerative Biology and Medicine, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
authors.affiliation: Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ushida
authors.affiliation: Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan; Institute for Biomedical Engineering Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Shinjuku, Tokyo 162-0041, Japan; Venetian Institute of Molecular Medicine, 35129 Padova, Italy. Electronic address: akimoto@m.u-tokyo.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Akimoto
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D014162:Transfection
chemical_list: D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse