Spatial regulation of brain derived neurotrophic factor (BDNF) expression in sensory neurons by microRNA-206
Date
2017
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
The 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.