MicroRNA miR-137 Regulates Neuronal Maturation by Targeting Ubiquitin Ligase Mind Bomb-1§

Authors


  • Author contributions: R.D.S.: concept and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; K.E.S.: collection and/or assembly of data, data analysis and interpretation, final approval of manuscript; R.L.P.: collection of data; X.L.: Provision of study material; W.G.: collection of data; M.P.: collection of data; Z.-Q.T.: collection of data; Y.L.: provision of study material; J.P.: provision of study material, A.B.: other (financial support and instruction of student); P.J.: concept and design, data analysis and interpretation, financial support, final approval of manuscript; X.Z.: concept and design, data analysis and interpretation, financial support, manuscript writing, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS April 21, 2010.

Abstract

The maturation of young neurons is regulated by complex mechanisms and dysregulation of this process is frequently found in neurodevepmental disorders. MicroRNAs have been implicated in several steps of neuronal maturation including dendritic and axonal growth, spine development, and synaptogenesis. We demonstrate that one brain-enriched microRNA, miR-137, has a significant role in regulating neuronal maturation. Overexpression of miR-137 inhibits dendritic morphogenesis, phenotypic maturation, and spine development both in brain and cultured primary neurons. On the other hand, a reduction in miR-137 had opposite effects. We further show that miR-137 targets the Mind bomb one (Mib1) protein through the conserved target site located in the 3′ untranslated region of Mib1 messenger RNA. Mib1 is an ubiquitin ligase known to be important for neurodevelopment. We show that exogenously expressed Mib1 could partially rescue the phenotypes associated with miR-137 overexpression. These results demonstrate a novel miRNA-mediated mechanism involving miR-137 and Mib1 that function to regulate neuronal maturation and dendritic morphogenesis during development. STEM Cells 2010;28:1060–1070

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