miR-375 inhibits differentiation of neurites by lowering HuD levels

Kotb Abdelmohsen, Emmette R. Hutchison, Eun Kyung Lee, Yuki Kuwano, Mihee M. Kim, Kiyoshi Masuda, Subramanya Srikantan, Sarah S. Subaran, Bernard S. Marasa, Mark P. Mattson, Myriam Gorospe

Research output: Contribution to journalArticle

Abstract

Neuronal development and plasticity are maintained by tightly regulated gene expression programs. Here, we report that the developmentally regulated microRNA miR-375 affects dendrite formation and maintenance. miR-375 overexpression in mouse hippocampus potently reduced dendrite density. We identified the predominantly neuronal RNA-binding protein HuD as a key effector of miR-375 influence on dendrite maintenance. Heterologous reporter analysis verified that miR-375 repressed HuD expression through a specific, evolutionarily conserved site on the HuD 3′ untranslated region. miR-375 overexpression lowered both HuD mRNA stability and translation and recapitulated the effects of HuD silencing, which reduced the levels of target proteins with key functions in neuronal signaling and cytoskeleton organization (N-cadherin, PSD-95, RhoA, NCAM1, and integrin α1). Moreover, the increase in neurite outgrowth after brain-derived neurotrophic factor (BDNF) treatment was diminished by miR-375 overexpression; this effect was rescued by reexpression of miR-375-refractory HuD. Our findings indicate that miR-375 modulates neuronal HuD expression and function, in turn affecting dendrite abundance.

Original languageEnglish (US)
Pages (from-to)4197-4210
Number of pages14
JournalMolecular and Cellular Biology
Volume30
Issue number17
DOIs
StatePublished - Sep 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Abdelmohsen, K., Hutchison, E. R., Lee, E. K., Kuwano, Y., Kim, M. M., Masuda, K., Srikantan, S., Subaran, S. S., Marasa, B. S., Mattson, M. P., & Gorospe, M. (2010). miR-375 inhibits differentiation of neurites by lowering HuD levels. Molecular and Cellular Biology, 30(17), 4197-4210. https://doi.org/10.1128/MCB.00316-10