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RNAi, Dicer, Argonaute, Doublecortin, miRNA-128, Adult neurogenesis
Abstract:
Background: Neurogenesis in the brain of adult mammals occurs throughout
life in two locations: the subventricular zone of the lateral ventricle
and the subgranular zone of the dentate gyrus in the hippocampus. RNA
interference mechanisms have emerged as critical regulators of neuronal
differentiation. However, to date, little is known about its function in
adult neurogenesis.
Results: Here we show that the RNA interference machinery regulates
Doublecortin levels and is associated with chromatin in differentiating
adult neural progenitors. Deletion of Dicer causes abnormal higher
levels of Doublecortin. The microRNA pathway plays an important role in
Doublecortin regulation. In particular miRNA-128 overexpression can
reduce Doublecortin levels in differentiating adult neural progenitors.
Conclusions: We conclude that the RNA interference components play an
important role, even through chromatin association, in regulating
neuron-specific gene expression programs.
