Spatial regulation of brain derived neurotrophic factor (BDNF) expression in sensory neurons by microRNA-206

Selva, EricaYoo, SoonmoonThe precise regulation of selective mRNA transport to its final destination and local translation is essential for normal neuronal function, morphological maintenance and regeneration after injury. Transcripts encoding brain-derived neurotrophic factor (BDNF) that regulates synaptic plasticity and memory are differentially localized in subcellular regions of hippocampal neurons. Given that differential distribution of the two different variants of BDNF mRNA’s 3¢ untranslated region (UTR) containing either a short (0.35kb) or a longer (2.9kb) form, I speculated that the longer 3¢UTR variant of BDNF mRNA is specifically localizing in distal axons of neurons and its local translation is regulated by small non-coding RNAs in a spatially specific manner. Using RT-PCR and fluorescent recovery after photobleaching (FRAP) approaches, I showed that BDNF mRNA with the longer 3¢UTR is endogenously present in distal axons of the sensory neurons, though the copy number is very low. Inconsistent with previous studies of dendrites of CNS neurons, the short 3¢UTR variant of BDNF mRNA targets a reporter mRNA to distal axons of sensory neurons. Bioinformatics analysis for predicting microRNAs (miRNAs) targeting the 3¢UTR of BDNF mRNA reveals that miRNA-206 may recognize and play regulatory roles in its gene expression. Results from target gene dual luciferase assay and overexpression of miR- 206 in F-11 cells show that miR-206 differentially down-regulates BDNF mRNA containing a longer 3¢UTR variant from that with a short form by targeting the predicted target site residing in the distal segment the longer form of the 3¢UTR. Western blots show that BDNF protein expression in DRG neurons (both cell body and axons) is decreased by 23% upon overexpression of miR-206. On the basis of these works presented here, I propose that different variants of BDNF mRNA that are differentially distributed to axons of sensory neurons are differentially regulated by miR-206.University of Delaware, Department of Biological SciencesM.S