Selective Localization of Arc mRNA in Dendrites Involves Activity- and Translation-Dependent mRNA Degradation
Selective Localization of Arc mRNA in Dendrites Involves Activity- and Translation-Dependent mRNA Degradation
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DOI：
10.1523/jneurosci.4944-13.2014
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发表时间：
2014-03-26
影响因子：
5.3
通讯作者：
Steward, Oswald
中科院分区：
文献类型：
--
作者：
Farris, Shannon;Lewandowski, Gail;Steward, Oswald
Arc是神经元mRNA中独特的立即早期基因，因为其转录物被转运到树突中并在激活的突触附近积累，推测其被局部翻译。这些品质使Arc在突触的活动依赖性修饰中发挥重要作用，但尚未完全理解，突触被认为是记忆储存的基础。在这里，我们表明，在大鼠体内，新合成的弧mRNA积累在激活的突触和突触活动，同时触发mRNA衰变，消除弧mRNA从非活性树突状结构域。Arc mRNA降解发生在整个树突中，需要NMDA受体激活和主动翻译。突触激活没有导致另一种树突mRNA（α CaMKII）的减少，表明树突中mRNA降解没有普遍激活。这些数据揭示了一种新的机制，用于控制树突内的mRNA分布，并强调活性依赖性的mRNA降解参与突触可塑性的调节过程。
Arc is an immediate early gene that is unique among neuronal mRNAs because its transcripts are transported into dendrites and accumulate near activated synapses, presumably to be translated locally. These qualities pose Arc as playing an important, yet not fully understood, role in the activity-dependent modifications of synapses that are thought to underlie memory storage. Here we show in vivo in rats that newly synthesized Arc mRNA accumulates at activated synapses and that synaptic activity simultaneously triggers mRNA decay that eliminates Arc mRNA from inactive dendritic domains. Arc mRNA degradation occurs throughout the dendrite and requires both NMDA receptor activation and active translation. Synaptic activation did not lead to decreases in another dendritic mRNA (alpha CaMKII), indicating that there is not a general activation of mRNA degradation in dendrites. These data reveal a novel mechanism for controlling mRNA distribution within dendrites and highlight activity-dependent mRNA degradation as a regulatory process involved in synaptic plasticity.