Regulation of NGF Signaling by an Axonal Untranslated mRNA
Regulation of NGF Signaling by an Axonal Untranslated mRNA
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DOI：
10.1016/j.neuron.2019.02.011
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发表时间：
2019-05-08
期刊：
影响因子：
16.2
通讯作者：
Riccio, Antonella
中科院分区：
文献类型：
--
作者：
Crerar, Hamish;Scott-Solomon, Emily;Riccio, Antonella
神经元是非常大且高度极化的细胞，需要细胞体和轴突之间进行长距离快速有效的通信。在周围神经元中，转录物沿着轴突运输到生长锥，在那里它们响应外部信号而快速翻译。在研究 Tp53inp2 这一在交感神经元轴突中高度表达和富集的转录本时，我们意外地发现 Tp53inp2 不被翻译。相反，转录本以独立于编码的方式支持轴突生长。越来越多的证据表明 mRNA 的功能可能与其编码能力无关；例如，充当功能相关蛋白质的支架。 Tp53inp2 转录本与神经生长因子 (NGF) 受体 TrkA 相互作用，调节 TrkA 内吞作用和信号传导。 Tp53inp2 的缺失会抑制体内轴突的生长，并且这种缺陷可以通过不可翻译的转录本来弥补。 Tp53inp2 是一种非典型 mRNA，通过以翻译独立的方式增强 NGF-TrkA 信号传导来调节轴突生长。
Neurons are extraordinarily large and highly polarized cells that require rapid and efficient communication between cell bodies and axons over long distances. In peripheral neurons, transcripts are transported along axons to growth cones, where they are rapidly translated in response to extrinsic signals. While studying Tp53inp2, a transcript highly expressed and enriched in sympathetic neuron axons, we unexpectedly discovered that Tp53inp2 is not translated. Instead, the transcript supports axon growth in a coding-independent manner. Increasing evidence indicates that mRNAs may function independently of their coding capacity; for example, acting as a scaffold for functionally related proteins. The Tp53inp2 transcript interacts with the nerve growth factor (NGF) receptor TrkA, regulating TrkA endocytosis and signaling. Deletion of Tp53inp2 inhibits axon growth in vivo, and the defects are rescued by a non-translatable form of the transcript. Tp53inp2 is an atypical mRNA that regulates axon growth by enhancing NGF-TrkA signaling in a translation-independent manner.