BioMedical Center, Medical Faculty, Ludwig Maximilians University, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany.
EMBL, Meyerhofstraße 1, 69117, Heidelberg, Germany.
Nat Commun. 2019 Jul 18;10(1):3178. doi: 10.1038/s41467-019-11123-x.
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.
mRNA 的运输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 如何精确地分拣到神经元突触仍然难以捉摸。在这里，我们使用 Rgs4 mRNA 通过 MS2 活细胞成像来研究 3'-UTR 依赖的运输。在树突中观察到的大多数 RNA 颗粒表现出 3'-UTR 不依赖的双向运输。重要的是，Rgs4 的 3'-UTR 导致顺行运输偏向，这需要 Staufen2 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 在树突中游动，允许与多个突触进行短暂的相互作用，这与寿司带模型一致。通过化学沉默或局部谷氨酸解笼来调节神经元活动，调节 3'-UTR 依赖的运输偏向和突触募集。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的方式进行翻译和突触重塑。
