Institute of Structural and Molecular Biology, University College London, UK.
The Francis Crick Institute, London, UK.
FEBS Lett. 2018 Sep;592(17):2932-2947. doi: 10.1002/1873-3468.13121. Epub 2018 Jun 16.
Establishing and maintaining the complex network of connections required for neuronal communication requires the transport and in situ translation of large groups of mRNAs to create local proteomes. In this Review, we discuss the regulation of local mRNA translation in neurons and the RNA-binding proteins that recognise RNA zipcode elements and connect the mRNAs to the cellular transport networks, as well as regulate their translation control. However, mRNA recognition by the regulatory proteins is mediated by the combinatorial action of multiple RNA-binding domains. This increases the specificity and affinity of the interaction, while allowing the protein to recognise a diverse set of targets and mediate a range of mechanisms for translational regulation. The structural and molecular understanding of the interactions can be used together with novel microscopy and transcriptome-wide data to build a mechanistic framework for the regulation of local mRNA translation.
建立和维持神经元通讯所需的复杂连接网络需要运输和原位翻译大量的 mRNA 以产生局部蛋白质组。在这篇综述中，我们讨论了神经元中局部 mRNA 翻译的调控以及识别 RNA 拉链码元件并将 mRNA 与细胞运输网络连接起来的 RNA 结合蛋白，以及调节其翻译控制的 RNA 结合蛋白。然而，调节蛋白对 mRNA 的识别是由多个 RNA 结合结构域的组合作用介导的。这增加了相互作用的特异性和亲和力，同时允许蛋白质识别多样化的靶标并介导一系列翻译调控机制。相互作用的结构和分子理解可以与新型显微镜和全转录组数据一起用于构建局部 mRNA 翻译调控的机制框架。
