Regulation of axon regeneration by the RNA repair and splicing pathway.
Regulation of axon regeneration by the RNA repair and splicing pathway.
复制标题
DOI：
10.1038/nn.4019
复制
发表时间：
2015-06
影响因子：
25
通讯作者：
Jan, Yuh Nung
中科院分区：
文献类型：
--
作者：
Song, Yuanquan;Sretavan, David;Salegio, Ernesto A.;Berg, Jim;Huang, Xi;Cheng, Tong;Xiong, Xin;Meltzer, Shan;Han, Chun;Trong-Tuong Nguyen;Bresnahan, Jacqueline C.;Beattie, Michael S.;Jan, Lily Yeh;Jan, Yuh Nung
控制神经元再生能力的机制很重要，但还没有被很好地理解。我们发现RTCA，RNA3‘-末端磷酸环化酶，是轴突再生的抑制因子。去除dRtca细胞--自主地促进果蝇中枢神经系统中轴突的再生，而它的过度表达则减少了外围的轴突再生。RTCA与RNA连接酶Rtcb及其催化剂Archease一起在RNA修复/剪接途径中发挥作用，该途径对应激诱导的mRNA剪接至关重要，包括XBP1，一种细胞应激传感器。DRtca和dArchase对XBP1的剪接有相反的作用，dArchase或XBP1的缺失阻碍了果蝇轴突的再生。此外，在体外培养的啮齿动物神经元中过表达哺乳动物RTCA降低了轴突的复杂性，而降低其功能则促进了小鼠视神经挤压后视网膜神经节细胞轴突的再生。因此，我们的研究将轴突再生与细胞应激和RNA代谢联系起来，揭示了治疗神经系统创伤的新的潜在治疗靶点。
Mechanisms governing a neuron’s regenerative ability are important but not well understood. We identified Rtca, RNA 3′-terminal phosphate cyclase, as an inhibitor for axon regeneration. Removal of dRtca cell-autonomously enhanced axon regrowth in the Drosophila central nervous system, whereas its overexpression reduced axon regeneration in the periphery. Rtca along with the RNA ligase Rtcb and its catalyst Archease operate in the RNA repair/splicing pathway important for stress induced mRNA splicing, including that of Xbp1, a cellular stress sensor. dRtca and dArchease had opposing effects on Xbp1 splicing, and deficiency of dArchease or Xbp1 impeded axon regeneration in Drosophila. Moreover, overexpressing mammalian Rtca in cultured rodent neurons reduced axonal complexity in vitro, whereas reducing its function promoted retinal ganglion cell axon regeneration after optic nerve crush in mice. Our study thus links axon regeneration to cellular stress and RNA metabolism, revealing new potential therapeutic targets for treating nervous system trauma.
登录
查看更多内容
影响因子：
5.7
作者：
Lu Y;Belin S;He Z
通讯作者：
He Z
影响因子：
5.3
作者：
Liu, X;Hawkes, E;Sretavan, DW
通讯作者：
Sretavan, DW
影响因子：
5.3
作者：
Awasaki, Takeshi;Lai, Sen-Lin;Lee, Tzumin
通讯作者：
Lee, Tzumin
影响因子：
64.8
作者：
Emoto, Kazuo;Parrish, Jay Z.;Jan, Yuh-Nung
通讯作者：
Jan, Yuh-Nung
DOI：
10.15252/embj.201490332
发表时间：
2014-12-17
期刊：
The EMBO journal
影响因子：
--
作者：
Jurkin J;Henkel T;Nielsen AF;Minnich M;Popow J;Kaufmann T;Heindl K;Hoffmann T;Busslinger M;Martinez J
通讯作者：
Martinez J