Think globally, translate locally: What mitotic spindles and neuronal synapses have in common

Early metazoan development is programmed by maternal mRNAs inherited by the egg at the time of fertilization. These mRNAs are not translated en masse at any one time or at any one place, but instead their expression is regulated both temporally and spatially. Recent evidence has shown that one maternal mRNA, cyclin B1, is concentrated on mitotic spindles in the early Xenopus embryo, where its translation is controlled by CPEB (cytoplasmic polyadenylation element binding protein), a sequence-specific RNA binding protein. Disruption of the spindle-associated translation of this mRNA results in a morphologically abnormal mitotic apparatus and inhibited cell division. Mammalian neurons, particularly in the synapto-dendritic compartment, also contain localized mRNAs such as that encoding α-CaMKII. Here, synaptic activation drives local translation, an event that is involved in synaptic plasticity and possibly long-term memory storage. Synaptic translation of α-CaMKII mRNA also appears to be controlled by CPEB, which is enriched in the postsynaptic density. Therefore, CPEB-controlled local translation may influence such seemingly disparate processes as the cell cycle and synaptic plasticity.

早期多细胞动物发育由受精阶段卵细胞继承的母体mRNA（maternal mRNA）编程调控。此类mRNA并非同时或在同一区域集体进行翻译，其表达受到严格的时空特异性调控。近期研究证据显示，母体mRNA中的细胞周期蛋白B1（cyclin B1）在非洲爪蟾胚胎（Xenopus embryo）的有丝分裂纺锤体（mitotic spindle）上富集，其翻译过程由胞质多聚腺苷酸化元件结合蛋白（CPEB，cytoplasmic polyadenylation element binding protein）调控——该蛋白是一种序列特异性RNA结合蛋白。破坏该mRNA的纺锤体关联翻译过程，会导致有丝分裂装置形态异常，并抑制细胞分裂。哺乳动物神经元，尤其是突触树突区室（synapto-dendritic compartment）中，同样存在局域化mRNA，例如编码α-钙/钙调蛋白依赖性蛋白激酶II（α-CaMKII）的mRNA。在此类神经元中，突触激活可驱动局部翻译，这一过程参与突触可塑性调控，且可能与长期记忆存储密切相关。α-钙/钙调蛋白依赖性蛋白激酶II mRNA的突触翻译过程，同样似乎受CPEB调控，该蛋白在突触后致密区（postsynaptic density）中高度富集。综上，受CPEB调控的局部翻译过程，可能对细胞周期与突触可塑性这两类看似截然不同的生命过程产生调控作用。