Bi Jing, Hu Xinli, Loh Horace H, Wei Li-Na
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St., SE, Minneapolis, MN 55455, USA.
Mol Pharmacol. 2003 Sep;64(3):594-9. doi: 10.1124/mol.64.3.594.
Three kappa-opioid receptor (KOR) mRNA isoforms have been detected in different parts of the central nervous system. At the cellular level, three KOR mRNA isoforms are also differentially distributed in the axons and cell bodies of adult mouse trigeminal neurons, as well as in the processes and cell bodies of differentiated P19 neurons. To determine the molecular basis underlying differential distribution of KOR mRNA isoforms, a GFP-fused RNA binding domain, MS2, was generated and used to trace movement of KOR mRNA tagged with the MS2-binding sequence in living neurons of dorsal root ganglia and in differentiated P19 neurons. The 5'- and 3'-untranslated regions (UTRs) of KOR, either alone or in combination, are able to mediate transport of mRNAs to processes of P19 neurons and axons of dorsal root ganglia. The efficiency of mRNA transport mediated by each 5'-UTR of KOR varies among the three isoforms; isoform A is most efficient. This study demonstrates the biological activity of the UTRs of KOR mRNA isoforms in directing differential transport of mRNA in mammalian neurons.
在中枢神经系统的不同部位已检测到三种κ-阿片受体(KOR)mRNA亚型。在细胞水平上,三种KOR mRNA亚型在成年小鼠三叉神经元的轴突和细胞体中,以及在分化的P19神经元的突起和细胞体中也呈差异分布。为了确定KOR mRNA亚型差异分布的分子基础,构建了一个与绿色荧光蛋白(GFP)融合的RNA结合结构域MS2,并用于追踪标记有MS2结合序列的KOR mRNA在背根神经节的活神经元和分化的P19神经元中的移动情况。KOR的5'非翻译区(UTR)和3'非翻译区单独或联合使用时,都能够介导mRNA向P19神经元的突起和背根神经节的轴突运输。KOR的每个5'UTR介导的mRNA运输效率在三种亚型中各不相同;A亚型效率最高。本研究证明了KOR mRNA亚型的UTR在指导哺乳动物神经元中mRNA差异运输方面的生物学活性。