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The intragenic microRNA miR199A1 in the dynamin 2 gene contributes to the pathology of X-linked centronuclear myopathy.
Chen, Xin; Gao, Yun-Qian; Zheng, Yan-Yan; Wang, Wei; Wang, Pei; Liang, Juan; Zhao, Wei; Tao, Tao; Sun, Jie; Wei, Lisha; Li, Yeqiong; Zhou, Yuwei; Gan, Zhenji; Zhang, Xuena; Chen, Hua-Qun; Zhu, Min-Sheng.
Afiliación
  • Chen X; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Gao YQ; Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development at the School of Life Sciences of Fudan University, Shanghai, China; Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai
  • Zheng YY; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Wang W; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Wang P; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Liang J; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Zhao W; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Tao T; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Sun J; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Wei L; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Li Y; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Zhou Y; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Gan Z; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China.
  • Zhang X; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China. Electronic address: zhangxn@nicemice.cn.
  • Chen HQ; College of Life Science, Nanjing Normal University, Nanjing, China. Electronic address: chenhuaqun@njnu.edu.cn.
  • Zhu MS; State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study and the Medical School, Nanjing University, Nanjing, China. Electronic address: zhums@nju.edu.cn.
J Biol Chem ; 295(26): 8656-8667, 2020 06 26.
Article en En | MEDLINE | ID: mdl-32354746
Mutations in the myotubularin 1 (MTM1) gene can cause the fatal disease X-linked centronuclear myopathy (XLCNM), but the underlying mechanism is incompletely understood. In this report, using an Mtm1-/y disease model, we found that expression of the intragenic microRNA miR-199a-1 is up-regulated along with that of its host gene, dynamin 2 (Dnm2), in XLCNM skeletal muscle. To assess the role of miR-199a-1 in XLCNM, we crossed miR-199a-1-/- with Mtm1-/y mice and found that the resultant miR-199a-1-Mtm1 double-knockout mice display markers of improved health, as evidenced by lifespans prolonged by 30% and improved muscle strength and histology. Mechanistic analyses showed that miR-199a-1 directly targets nonmuscle myosin IIA (NM IIA) expression and, hence, inhibits muscle postnatal development as well as muscle maturation. Further analysis revealed that increased expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) up-regulates Dnm2/miR-199a-1 expression in XLCNM muscle. Our results suggest that miR-199a-1 has a critical role in XLCNM pathology and imply that this microRNA could be targeted in therapies to manage XLCNM.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Miopatías Estructurales Congénitas / Dinamina II / MicroARNs Límite: Animals Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Miopatías Estructurales Congénitas / Dinamina II / MicroARNs Límite: Animals Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: China