The dynamic recruitment of TRBP to neuronal membranes mediates dendritogenesis during development. The dynamic recruitment of TRBP to neuronal membranes mediates dendritogenesis during development

MicroRNAs are important regulators of local protein synthesis during neuronal development. We investigated the dynamic regulation of microRNA production and found that the majority of the microRNA-generating complex, consisting of Dicer, TRBP and PACT, specifically associates with intra-cellular membranes in developing neurons. Stimulation with brain-derived neurotrophic factor (BDNF), which promotes dendritogenesis, caused the re-distribution of TRBP from the endoplasmic reticulum into the cytoplasm, and its dissociation from Dicer, in a Ca2+-dependent manner. As a result, the processing of a subset of neuronal precursor microRNAs, among them the dendrite-enriched pre-miR16, was impaired. Decreased production of miR-16-5p, which targeted the BDNF mRNA itself, was rescued by expression of a membrane-targeted TRBP. Moreover, miR-16-5p or membrane-targeted TRBP expression blocked BDNF-induced dendritogenesis, demonstrating the importance of neuronal TRBP dynamics for activity-dependent neuronal development. We propose that neurons employ specialized mechanisms to modulate local gene expression in dendrites, via the dynamic regulation of microRNA biogenesis factors at intracellular membranes of the endoplasmic reticulum, which in turn is crucial for neuronal dendrite complexity and therefore neuronal circuit formation and function. Overall design: miRNA expression profiles of control- and BDNF-treated DIV rat cortical neurons were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.