Abstract
Distinct subcellular localization and subsequent translational control of 3′ UTR variants of mRNA encoding brain‐derived neurotrophic factor (BDNF) are critical for the development and plasticity of neurons. Although the processes that lead to preferential localization of BDNF have been well studied, it is still not clear how neurons ensure differential BDNF production in a spatial‐specific manner. Here, we identified that microRNA (miRNA)‐206 has the potential to specifically regulate BDNF with a long 3′ UTR without affecting its short 3′ UTR counterpart. Overexpression of miRNA‐206 in sensory neurons resulted in a 30% and 45% reduction of BDNF protein expression in the cell bodies and axons, respectively. The work described in the present study indicates that miRNAs can differentially and specifically regulate the expression of transcript variants with different localization patterns.
Highlights
Brain-derived neurotrophic factor (BDNF) is a secreted protein of the neurotrophin family that plays crucial roles in the development and survival of neurons, growth of neuronal processes and synaptic plasticity [1–4]
Lee et al [16] showed that aberrantly high levels of miRNA-206 in Alzheimer diseased brains are directly involved in the pathogenesis of Alzheimer disease by targeting the 30 UTR of brain-derived neurotrophic factor (BDNF) mRNA, suggesting that BDNF expression is post-transcriptionally regulated by miRNA-206
To re-evaluate subcellular localization of the long 30 UTR variant of BDNF mRNA in distal axons of dorsal root ganglion (DRG) neurons in vivo, sciatic nerve axoplasm was mechanically extracted from the nerve of adult rats using the mechanical squeezing method that we optimized previously [17]
Summary
Brain-derived neurotrophic factor (BDNF) is a secreted protein of the neurotrophin family that plays crucial roles in the development and survival of neurons, growth of neuronal processes and synaptic plasticity [1–4]. The short 30 UTR variant of BDNF mRNA is reported to be restricted in the soma and the long variant is preferentially transported to dendrites, contributing to the activity-dependent rapid increase in local expression [12] These studies indicate that the 30 UTR of BDNF mRNA may play important roles in both mRNA localization and regulation of translation. Small non-coding RNAs such as microRNAs (miRNAs) have been found to mediate the control of key genes involved in the nervous system, suggesting that miRNAs have a role as key regulators in BDNF expression at the post-transcriptional level It is still unclear how translation of these 30 UTR variants of the transcripts is differentially regulated in a spatial-specific manner. We hypothesized that the long 30 UTR variant of BDNF mRNA could be subjected to the differential regulation by specific miRNAs from the counterpart with a short 30 UTR in a spatial-specific manner
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