ONO Masafumi
   Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine
Article types Original article
Language English
Peer review Peer reviewed
Title Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers.
Journal Formal name:Molecular and cellular biology
Abbreviation:Mol Cell Biol
ISSN code:10985549/02707306
Domestic / ForeginForegin
Volume, Issue, Page 35(13),pp.2295-308
Author and coauthor Todaka Hiroshi, Higuchi Takuma, Yagyu Ken-ichi, Sugiyama Yasunori, Yamaguchi Fumika, Morisawa Keiko, Ono Masafumi, Fukushima Atsuki, Tsuda Masayuki, Taniguchi Taketoshi, Sakamoto Shuji
Publication date 2015/07
Summary 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