Abstract |
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.
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Authors | Hiroshi Todaka, Takuma Higuchi, Ken-ichi Yagyu, Yasunori Sugiyama, Fumika Yamaguchi, Keiko Morisawa, Masafumi Ono, Atsuki Fukushima, Masayuki Tsuda, Taketoshi Taniguchi, Shuji Sakamoto |
Journal | Molecular and cellular biology
(Mol Cell Biol)
Vol. 35
Issue 13
Pg. 2295-308
(Jul 2015)
ISSN: 1098-5549 [Electronic] United States |
PMID | 25918244
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015, American Society for Microbiology. All Rights Reserved. |
Chemical References |
- MicroRNAs
- Mirn133 microRNA, mouse
- Nuclear Factor 45 Protein
- Nuclear Factor 90 Proteins
- Dynamin II
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Topics |
- Animals
- Cell Line
- Dynamin II
(genetics, metabolism)
- Female
- Gene Expression Regulation
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- MicroRNAs
(genetics, metabolism)
- Muscle, Skeletal
(metabolism, pathology)
- Muscular Atrophy
(genetics, metabolism, pathology)
- Nuclear Factor 45 Protein
(genetics, metabolism)
- Nuclear Factor 90 Proteins
(genetics, metabolism)
- Up-Regulation
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