Kim Hak Hee, Kim Paul, Phay Monichan, Yoo Soonmoon
Nemours Biomedical Research, Alfred I. DuPont Hospital for Children, Wilmington, Delaware, USA.
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
J Neurochem. 2015 Jul;134(2):193-9. doi: 10.1111/jnc.13140. Epub 2015 May 23.
A set of specific precursor microRNAs (pre-miRNAs) are reported to localize into neuronal dendrites, where they could be processed locally to control synaptic protein synthesis and plasticity. However, it is not clear whether specific pre-miRNAs are also transported into distal axons to autonomously regulate intra-axonal protein synthesis. Here, we show that a subset of pre-miRNAs, whose mature miRNAs are enriched in axonal compartment of sympathetic neurons, are present in axons of neurons both in vivo and in vitro by quantitative PCR and by in situ hybridization. Some pre-miRNAs (let 7c-a and pre-miRs-16, 23a, 25, 125b-1, 433, and 541) showed elevated axonal levels, while others (pre-miRs-138-2, 185, and 221) were decreased in axonal levels following injury. Dicer and KSRP proteins are also present in distal axons, but Drosha is found restricted to the cell body. These findings suggest that specific pre-miRNAs are selected for localization into distal axons of sensory neurons and are presumably processed to mature miRNAs in response to extracellular stimuli. This study supports the notion that local miRNA biogenesis effectively provides another level of temporal control for local protein synthesis in axons.
据报道，一组特定的前体微小RNA（pre-miRNA）定位于神经元树突中，在那里它们可以在局部进行加工，以控制突触蛋白合成和可塑性。然而，尚不清楚特定的pre-miRNA是否也被转运到轴突远端，以自主调节轴突内蛋白质合成。在这里，我们通过定量PCR和原位杂交表明，在体内和体外，神经元轴突中都存在一部分pre-miRNA，其成熟的miRNA在交感神经元的轴突部分富集。一些pre-miRNA（let 7c-a和pre-miRs-16、23a、25、125b-1、433和541）的轴突水平升高，而其他一些（pre-miRs-138-2、185和221）在损伤后轴突水平降低。Dicer和KSRP蛋白也存在于轴突远端，但Drosha仅局限于细胞体。这些发现表明，特定的pre-miRNA被选择定位于感觉神经元的轴突远端，并可能在细胞外刺激下被加工成成熟的miRNA。这项研究支持了这样一种观点，即局部miRNA生物合成有效地为轴突内的局部蛋白质合成提供了另一个时间控制水平。
