Live cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
Live cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
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DOI：
10.1038/s41467-019-11123-x
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发表时间：
2019-07-18
影响因子：
16.6
通讯作者：
Kiebler, Michael A.
中科院分区：
文献类型：
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作者：
Bauer, Karl E.;Segura, Inmaculada;Kiebler, Michael A.
mRNA转运将翻译限制在特定的亚细胞位置，这是许多细胞功能的基础。然而，mRNA分选到神经元突触的精确过程仍然难以捉摸。在这里，我们使用Rgs 4 mRNA通过MS 2活细胞成像来研究3 '-UTR依赖性转运。大多数观察到的RNA颗粒在树突中显示3 '-UTR非依赖性双向转运。重要的是，Rgs 4 3 '-UTR导致顺行转运偏好，这需要Staufen 2蛋白。此外，3 '-UTR介导动态的、持续的mRNA募集到突触。高时间分辨率的可视化使我们能够显示mRNA巡逻树突，允许与多个突触的短暂相互作用，与寿司带模型一致。通过化学沉默或局部谷氨酸释放来调节神经元活性调节3 '-UTR依赖性转运偏倚和突触募集。这种动态和可逆的mRNA募集到活跃的突触将允许以空间和时间适应性的方式进行翻译和突触重塑。
mRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. However, the precise process of mRNA sorting to synapses in neurons remains elusive. Here we use Rgs4 mRNA to investigate 3'-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules display 3'-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3'-UTR causes an anterograde transport bias, which requires the Staufen2 protein. Moreover, the 3'-UTR mediates dynamic, sustained mRNA recruitment to synapses. Visualization at high temporal resolution enables us to show mRNA patrolling dendrites, allowing transient interaction with multiple synapses, in agreement with the sushi-belt model. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3'-UTR-dependent transport bias and synaptic recruitment. This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner.