MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1.
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.
Smrt
Richard D
RD
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Szulwach
Keith E
KE
Pfeiffer
Rebecca L
RL
Li
Xuekun
X
Guo
Weixiang
W
Pathania
Manavendra
M
Teng
Zhao-Qian
ZQ
Luo
Yuping
Y
Peng
Junmin
J
Bordey
Angelique
A
Jin
Peng
P
Zhao
Xinyu
X
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D014176:Protein Biosynthesis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
C551799:MIRN137 microRNA, mouse; D035683:MicroRNAs; C470629:MIB1 protein, mouse; D044767:Ubiquitin-Protein Ligases