Translational suppression of atrophic regulators by MicroRNA-23a integrates resistance to skeletal muscle atrophy

Shogo Wada, Yoshio Kato, Mitsuharu Okutsu, Shigeru Miyaki, Katsuhiko Suzuki, Zhen Yan, Stefano Schiaffino, Hiroshi Asahara, Takashi Ushida, Takayuki Akimoto

Research output: Contribution to journalArticle

96 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)38456-38465
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number44
DOIs
Publication statusPublished - 2011 Nov 4

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Muscular Atrophy
MicroRNAs
Muscle
Skeletal Muscle
Ligases
Ubiquitin
Muscles
Proteolysis
Fingers
3' Untranslated Regions
Transgenic Mice
Atrophy
Degradation
Glucocorticoids
Proteins
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Translational suppression of atrophic regulators by MicroRNA-23a integrates resistance to skeletal muscle atrophy. / Wada, Shogo; Kato, Yoshio; Okutsu, Mitsuharu; Miyaki, Shigeru; Suzuki, Katsuhiko; Yan, Zhen; Schiaffino, Stefano; Asahara, Hiroshi; Ushida, Takashi; Akimoto, Takayuki.

In: Journal of Biological Chemistry, Vol. 286, No. 44, 04.11.2011, p. 38456-38465.

Research output: Contribution to journalArticle

Wada, Shogo ; Kato, Yoshio ; Okutsu, Mitsuharu ; Miyaki, Shigeru ; Suzuki, Katsuhiko ; Yan, Zhen ; Schiaffino, Stefano ; Asahara, Hiroshi ; Ushida, Takashi ; Akimoto, Takayuki. / Translational suppression of atrophic regulators by MicroRNA-23a integrates resistance to skeletal muscle atrophy. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 44. pp. 38456-38465.
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