Identification of a cis-acting element that localizes mRNA to synapses

Identification of a cis-acting element that localizes mRNA to synapses
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DOI:
10.1073/pnas.1116269109
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发表时间:
2012-03-20
影响因子:
11.1
通讯作者:
Martin, Kelsey C.
Martin, Kelsey C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Meer, Elliott J.;Wang, Dan Ohtan;Martin, Kelsey C.

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信使RNA(mRNA)的定位和调控翻译可以在空间上将基因表达限制在单个神经元形成的数千个突触区室中的每一个。虽然顺式作用RNA元件已被证明可以指导mRNA从索马定位到神经元过程中,但对将转录物特异性靶向突触的信号知之甚少。在海兔感觉运动神经元培养物中,突触形成迅速将编码肽神经递质传感素的mRNA从神经炎轴重新分配到突触中。我们发现感觉素mRNA从索马体到轴突的输出和到突触的定位受不同的信号控制。3' UTR足以输出到远端神经突中,而5' UTR是突触处报告mRNA浓缩所需的。我们已经在传感蛋白的5'非翻译区鉴定了一个66-nt的元件,它对于突触mRNA的定位是必要的和足够的。突变和化学探测分析与二级结构在此过程中的作用一致。
Messenger RNA (mRNA) localization and regulated translation can spatially restrict gene expression to each of the thousands of synaptic compartments formed by a single neuron. Although cis-acting RNA elements have been shown to direct localization of mRNAs from the soma into neuronal processes, less is known about signals that target transcripts specifically to synapses. In Aplysia sensory-motor neuronal cultures, synapse formation rapidly redistributes the mRNA encoding the peptide neurotransmitter sensorin from neuritic shafts into synapses. We find that the export of sensorin mRNA from soma to neurite and the localization to synapse are controlled by distinct signals. The 3' UTR is sufficient for export into distal neurites, whereas the 5' UTR is required for concentration of reporter mRNA at synapses. We have identified a 66-nt element in the 5' UTR of sensorin that is necessary and sufficient for synaptic mRNA localization. Mutational and chemical probing analyses are consistent with a role for secondary structure in this process.