RNA ligation in neurons by RtcB inhibits axon regeneration
RNA ligation in neurons by RtcB inhibits axon regeneration
复制标题
DOI：
10.1073/pnas.1502948112
复制
发表时间：
2015-07-07
影响因子：
11.1
通讯作者：
Hammarlund, Marc
中科院分区：
文献类型：
--
作者：
Kosmaczewski, Sara Guckian;Han, Sung Min;Hammarlund, Marc
RNA连接酶RtcB的活性仅具有两种已知功能：内含子去除后的tRNA连接和未折叠蛋白质反应激活期间的XBP1 mRNA连接。在这里，我们发现RtcB在神经元中起作用，抑制神经损伤后的轴突再生。RtcB的这种功能不依赖于其在tRNA连接和未折叠蛋白反应中的基础活性。此外，轴突再生的抑制是独立的RtcB辅因子archease。最后，神经损伤后，RtcB在轴突末端富集。我们的数据表明，神经元已经增选了一个古老的RNA修饰机制来调节特定的和动态的功能，并确定神经元RtcB活性作为神经元生长潜力的关键调节因子。
Activity of the RNA ligase RtcB has only two known functions: tRNA ligation after intron removal and XBP1 mRNA ligation during activation of the unfolded protein response. Here, we show that RtcB acts in neurons to inhibit axon regeneration after nerve injury. This function of RtcB is independent of its basal activities in tRNA ligation and the unfolded protein response. Furthermore, inhibition of axon regeneration is independent of the RtcB cofactor archease. Finally, RtcB is enriched at axon termini after nerve injury. Our data indicate that neurons have co-opted an ancient RNA modification mechanism to regulate specific and dynamic functions and identify neuronal RtcB activity as a critical regulator of neuronal growth potential.