MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase Mind Bomb-1

• Type of Material: Article
• Authors: Richard D. Smrt, University of New Mexico; Keith E. Szulwach, Emory University; Rebecca L. Pfeiffer, University of New Mexico; Xuekun Li, University of New Mexico; Weixiang Guo, University of New Mexico; Manavendra Pathania, Yale University; Zhao-Qian Teng, University of New Mexico; Yuping Luo, University of New Mexico; Junmin Peng, Emory University; Angelique Bordey, Yale University; Peng Jin, Emory University; Xinyu Zhao, University of New Mexico
• Language: English
• Date: 2010-06
• Publisher: AlphaMed Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 AlphaMed Press
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/stem.431/abstract
• Title of Journal or Parent Work: STEM CELLS
• ISSN: 1066-5099
• Volume: 28
• Issue: 6
• Start Page: 1060
• End Page: 1070
• Grant/Funding Information: P.J. is the recipient of a Beckman Young Investigator Award, Basil O’Connor Scholar Research Award, and Alfred P. Sloan Research Fellow in Neuroscience.; X.L. was a recipient of the Autism Speaks Postdoctoral Fellowship.; This work was supported by grants from NIH (MH080434, MH07897) and International Rett Syndrome Foundation (IRSF) to XZ; a Minority Supplement (MH080434) to RDS; Institutional Minority Student Development program (IMSD, NIH 2R25GM060201-09) to RLP; grants from NIH (NS051630 and MH076090) and IRSF to PJ.
• Keywords: adult neurogenesis; neuronal maturation; dendritic development; miR-137; microRNA; neural stem cells
• Research Categories: Biology, Neuroscience; Biology, Genetics

Abstract

A final step of neurogenesis is the maturation of young neurons, which is regulated by complex mechanisms and dysregulation of this process is frequently found in neurodevelopmental 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 Drosophila Mib1 protein through the conserved target site located in the 3′ untranslated region of Mib1 mRNA. 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.