Cosker Katharina E, Fenstermacher Sara J, Pazyra-Murphy Maria F, Elliott Hunter L, Segal Rosalind A
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Nat Neurosci. 2016 May;19(5):690-696. doi: 10.1038/nn.4280. Epub 2016 Mar 28.
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, poly-glutamine rich) as an RBP that binds and regulates multiple mRNAs in dorsal root ganglion sensory neurons and thereby promotes neurotrophin-dependent axonal viability. SFPQ acts in nuclei, cytoplasm and axons to regulate functionally related mRNAs essential for axon survival. Notably, SFPQ is required for coassembly of LaminB2 (Lmnb2) and Bclw (Bcl2l2) mRNAs in 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.
为实现基因表达精确的时空模式，RNA结合蛋白（RBPs）指导靶mRNA的核加工、细胞内运输及局部翻译。在神经元中，RBPs将靶mRNA运输至远端轴突和树突中的翻译位点。然而，在这些形态复杂的细胞中，单个RBP是否协调调控多个mRNA尚不清楚。在此，我们鉴定出SFPQ（富含多聚谷氨酰胺的剪接因子）为一种RBP，其在背根神经节感觉神经元中结合并调控多个mRNA，从而促进神经营养因子依赖的轴突存活。SFPQ在细胞核、细胞质和轴突中发挥作用，调控轴突存活所必需的功能相关mRNA。值得注意的是，SFPQ是LaminB2（Lmnb2）和Bclw（Bcl2l2）mRNA在RNA颗粒中共同组装以及这些mRNA轴突运输所必需的。这些数据共同表明，SFPQ协调一个新鉴定的对轴突存活至关重要的RNA调控子的空间基因表达。
