Systematic name M2509
Brief description Major ELAVL4 [GeneID=1996] associated mRNAs encoding proteins with functions in neuronal physiology.
Full description or 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 alpha1). 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 20584986   Authors: Abdelmohsen K,Hutchison ER,Lee EK,Kuwano Y,Kim MM,Masuda K,Srikantan S,Subaran SS,Marasa BS,Mattson MP,Gorospe M
Exact source Fig. 6A
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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