オノ　マサフミ   Ono Masafumi   小野　正文    所属   医学部 医学科（附属足立医療センター）    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers.
掲載誌名	正式名：Molecular and cellular biology 略　 称：Mol Cell Biol ISSNコード：10985549/02707306
掲載区分	国外
巻・号・頁	35(13),pp.2295-308
著者・共著者	Todaka Hiroshi, Higuchi Takuma, Yagyu Ken-ichi, Sugiyama Yasunori, Yamaguchi Fumika, Morisawa Keiko, Ono Masafumi, Fukushima Atsuki, Tsuda Masayuki, Taniguchi Taketoshi, Sakamoto Shuji
発行年月	2015/07
概要	MicroRNAs (miRNAs) are involved in the progression and suppression of various diseases through translational inhibition of target mRNAs. Therefore, the alteration of miRNA biogenesis induces several diseases. The nuclear factor 90 (NF90)-NF45 complex is known as a negative regulator in miRNA biogenesis. Here, we showed that NF90-NF45 double-transgenic (dbTg) mice develop skeletal muscle atrophy and centronuclear muscle fibers in adulthood. Subsequently, we found that the levels of myogenic miRNAs, including miRNA 133a (miR-133a), which promote muscle maturation, were significantly decreased in the skeletal muscle of NF90-NF45 dbTg mice compared with those in wild-type mice. However, levels of primary transcripts of the miRNAs (pri-miRNAs) were clearly elevated in NF90-NF45 dbTg mice. This result indicated that the NF90-NF45 complex suppressed miRNA production through inhibition of pri-miRNA processing. This finding was supported by the fact that processing of pri-miRNA 133a-1 (pri-miR-133a-1) was inhibited via binding of NF90-NF45 to the pri-miRNA. Finally, the level of dynamin 2, a causative gene of centronuclear myopathy and concomitantly a target of miR-133a, was elevated in the skeletal muscle of NF90-NF45 dbTg mice. Taken together, we conclude that the NF90-NF45 complex induces centronuclear myopathy through increased dynamin 2 expression by an NF90-NF45-induced reduction of miR-133a expression in vivo.
DOI	10.1128/MCB.01297-14
PMID	25918244