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: Shogo Wada, Yoshio Kato, Mitsuharu Okutsu, Shigeru Miyaki, Katsuhiko Suzuki, Zhen Yan, Stefano Schiaffino, Hiroshi Asahara, Takashi Ushida, Takayuki Akimoto
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 44 Pg. 38456-38465 (Nov 04 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 21926429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• Mirn23b microRNA, mouse

Topics

• Animals
• Base Sequence
• Cell Line
• Gene Expression Regulation
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• MicroRNAs (metabolism)
• Molecular Sequence Data
• Muscle, Skeletal (metabolism)
• Muscular Atrophy (genetics, metabolism)
• Protein Biosynthesis
• Transfection