The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability.

The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability.
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DOI:
10.1038/nn.4280
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发表时间:
2016-05
影响因子:
25
通讯作者:
Segal RA
Segal RA
中科院分区:
医学1区
文献类型:
--
作者:
Cosker KE;Fenstermacher SJ;Pazyra-Murphy MF;Elliott HL;Segal RA

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为了实现基因表达的精确时空模式,RNA结合蛋白(RBP)引导靶mRNA的核加工、细胞内运输和局部翻译。在神经元中,RBP引导靶mRNA转运到远端轴突和树突中的翻译位点。然而,目前还不知道是否一个单独的RBP协调调节这些形态复杂的细胞内的多个mRNA。在这里,我们确定SFPQ(剪接因子,脯氨酸-谷氨酰胺丰富)作为RBP结合和调节背根神经节(DRG)感觉神经元中的多个mRNA,从而促进神经营养因子依赖性轴突活力。SFPQ在细胞核、细胞质和轴突内起作用,调节轴突存活所必需的多种功能相关的mRNA。值得注意的是,SFPQ是RNA颗粒内laminb 2和bclw的共组装以及这些mRNA的轴突运输所必需的。总之,这些数据表明,SFPQ编排空间基因表达的一个新发现的RNA调节子轴突活力所必需的。
To achieve accurate spatiotemporal patterns of gene expression, RNA-binding proteins (RBPs) guide nuclear processing, intracellular trafficking, and local translation of target mRNAs. In neurons, RBPs direct transport of target mRNAs to sites of translation in remote axons and dendrites. However, it is not known whether an individual RBP coordinately regulates multiple mRNAs within these morphologically complex cells. Here we identify SFPQ (Splicing factor, proline-glutamine rich) as an RBP that binds and regulates multiple mRNAs in dorsal root ganglion (DRG) sensory neurons and thereby promotes neurotrophin-dependent axonal viability. SFPQ acts within nuclei, cytoplasm and axons to regulate multiple functionally related mRNAs essential for axon survival. Notably SFPQ is required for co-assembly of laminb2 and bclw within RNA granules and for axonal trafficking of these mRNAs. Together these data demonstrate that SFPQ orchestrates spatial gene expression of a newly identified RNA regulon essential for axonal viability.
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