Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling.

Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling.
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DOI:
10.1083/jcb.201911078
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发表时间:
2021-02-01
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Araki T
Araki T
中科院分区:
其他
文献类型:
--
作者:
Wakatsuki S;Takahashi Y;Shibata M;Adachi N;Numakawa T;Kunugi H;Araki T

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小型非编码穹窿 RNA 是穹窿复合物的组成部分,穹窿复合物是大多数真核生物中发现的核糖核蛋白复合物。若槻等人。表明穹窿RNA通过调节神经元中的MAPK信号通路作为突触发生的核糖调节剂。小非编码穹窿 RNA (vtRNA) 是穹窿复合物的组成部分,穹窿复合物是大多数真核生物中发现的核糖核蛋白复合物。新的证据表明,当与穹窿复合体无关时,vtRNA 可能参与多种细胞功能的调节。在这里,我们证明了 vtRNA 在突触发生中的新作用。使用体外突触形成模型,我们发现鼠 vtRNA (mvtRNA) 通过调节 MAPK 信号通路促进突触形成。 mvtRNA 作为穹窿复合体的一部分被运输到神经突的远端区域。有趣的是,mvtRNA 通过有丝分裂激酶 Aurora-A 依赖性 MVP(穹窿复合体的主要蛋白质成分)的磷酸化从神经突中的穹窿复合体中释放。 mvtRNA 结合并激活 MEK1,从而增强神经突中 MEK1 介导的 ERK 激活。这些结果表明 vtRNA 存在 MAPK 信号通路的调节机制,作为突触形成的新分子基础。
The small noncoding vault RNA is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. Wakatsuki et al. show that vault RNA functions as a riboregulator of synaptogenesis by modulating the MAPK signaling pathway in neurons. The small noncoding vault RNA (vtRNA) is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. Emerging evidence suggests that vtRNAs may be involved in the regulation of a variety of cellular functions when unassociated with the vault complex. Here, we demonstrate a novel role for vtRNA in synaptogenesis. Using an in vitro synapse formation model, we show that murine vtRNA (mvtRNA) promotes synapse formation by modulating the MAPK signaling pathway. mvtRNA is transported to the distal region of neurites as part of the vault complex. Interestingly, mvtRNA is released from the vault complex in the neurite by a mitotic kinase Aurora-A–dependent phosphorylation of MVP, a major protein component of the vault complex. mvtRNA binds to and activates MEK1 and thereby enhances MEK1-mediated ERK activation in neurites. These results suggest the existence of a regulatory mechanism of the MAPK signaling pathway by vtRNAs as a new molecular basis for synapse formation.
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