Gomes Cynthia, Merianda Tanuja T, Lee Seung Joon, Yoo Soonmoon, Twiss Jeffery L
Department of Biology, Drexel University, Philadelphia, Pennsylvania, 19104.
Dev Neurobiol. 2014 Mar;74(3):218-32. doi: 10.1002/dneu.22123. Epub 2013 Oct 7.
Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in cell body responses to axotomy. Recent studies have begun to identify the protein products that contribute to these autonomous responses of axons. In the peripheral nervous system, intra-axonal protein synthesis has been implicated in the localized in vivo responses to neuropathic stimuli, and there is emerging evidence for protein synthesis in CNS axons in vivo. Despite that hundreds of mRNAs have now been shown to localize into the axonal compartment, knowledge of what RNA binding proteins are responsible for this is quite limited. Here, we review the current state of knowledge of RNA transport mechanisms and highlight recently uncovered mechanisms for dynamically altering the axonal transcriptome. Both changes in the levels or activities of components of the RNA transport apparatus and alterations in transcription of transported mRNAs can effectively shift the axonal mRNA population. Consistent with this, the axonal RNA population shifts with development, with changes in growth state, and in response to extracellular stimulation. Each of these events must impact the transcriptional and transport apparatuses of the neuron, thus directly and indirectly modifying the axonal transcriptome.
轴突蛋白合成已被证明在发育性生长和再生性生长中发挥作用,以及在细胞体对轴突切断的反应中发挥作用。最近的研究已开始鉴定促成轴突这些自主反应的蛋白质产物。在周围神经系统中,轴突内蛋白合成与对神经性刺激的局部体内反应有关,并且有新证据表明中枢神经系统轴突在体内存在蛋白合成。尽管现在已有数百种mRNA被证明定位于轴突区室,但对于负责此过程的RNA结合蛋白的了解却相当有限。在此,我们综述了RNA转运机制的当前知识状态,并强调了最近发现的动态改变轴突转录组的机制。RNA转运装置组分的水平或活性变化以及被转运mRNA转录的改变均可有效改变轴突mRNA群体。与此一致的是,轴突RNA群体随发育、生长状态变化以及对细胞外刺激的反应而改变。这些事件中的每一个都必然影响神经元的转录和转运装置,从而直接和间接地修饰轴突转录组。