Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1381, USA.
Mol Cell Neurosci. 2010 Apr;43(4):422-30. doi: 10.1016/j.mcn.2010.01.009. Epub 2010 Feb 6.
Trafficking and local translation of axonal mRNAs play a critical role in the development and function of this neuronal subcellular structural domain. In this report, we studied cytochrome c oxidase subunit IV (COXIV) mRNA trafficking into distal axons of primary superior cervical ganglia (SCG) neurons, and provided evidence that axonal trafficking and mitochondrial association of the mRNA are mediated by an element located in a 38bp-long, hairpin-loop forming region within the 3'UTR of the transcript. Our results also suggest that suppression of local translation of COXIV mRNA results in significant attenuation of axonal elongation. Taken together, the results provide the first evidence for the existence of a cis-acting axonal transport element within a nuclear-encoding mitochondrial gene, and demonstrate the importance of the axonal trafficking and local translation of nuclear-encoded mitochondrial mRNAs in axonal growth.
轴突 mRNA 的贩运和局部翻译在这个神经元亚细胞结构域的发育和功能中起着关键作用。在本报告中,我们研究了细胞色素 c 氧化酶亚基 IV(COXIV)mRNA 向初级颈上交感神经节(SCG)神经元的远端轴突的贩运,并提供了证据表明,mRNA 的轴突贩运和线粒体缔合是由位于转录本 3'UTR 内的 38bp 长发夹环形成区域中的一个元件介导的。我们的结果还表明,抑制 COXIV mRNA 的局部翻译会导致轴突伸长显著减弱。总之,这些结果首次提供了核编码线粒体基因内存在顺式作用的轴突运输元件的证据,并证明了核编码线粒体 mRNA 的轴突运输和局部翻译在轴突生长中的重要性。