Gene splicing modulates the potency of cell death effectors, alters neuropathological disease processes, influences neuronal recovery, but may also direct distinct mechanisms of secondary brain injury. Therapeutic targeting of RNA splicing is a promising avenue for next-generation CNS treatments. RNA-binding proteins (RBPs) regulate a variety of RNA species and are prime candidates in the hunt for druggable targets to manipulate and tailor gene-splicing responses in the brain. RBPs preferentially recognize unique consensus sequences in targeted mRNAs. Also, RBPs often contain multiple RNA-binding domains (RBDs)—each having a unique consensus sequence—suggesting the possibility that drugs could be developed to block individual functional domains, increasing the precision of RBP-targeting therapies. Empirical characterization of most RBPs is lacking and represents a major barrier to advance this emerging therapeutic area. There is a paucity of data on the role of RBPs in the brain including, identification of their unique mRNA targets, defining how CNS insults affect their levels and elucidating which RBPs (and individual domains within) to target to improve neurological outcomes. This review focuses on the state-of-the-art of the RBP tumor suppressor RNA binding motif 5 (RBM5) in the CNS. We discuss its potent pro-death roles in cancer, which motivated our interest to study it in the brain. We review recent studies showing that RBM5 levels are increased after CNS trauma and that it promotes neuronal death in vitro. Finally, we conclude with recent reports on the first set of RBM5 regulated genes identified in the intact brain, and discuss how those findings provide new clues germane to its potential function(s) in the CNS, and pose new questions on its therapeutic utility to mitigate CNS injury.

基因剪接调节细胞死亡效应子的效力，改变神经病理学疾病过程，影响神经元恢复，但也可能指导继发性脑损伤的独特机制。RNA剪接的靶向治疗是下一代CNS治疗的有希望的途径。RNA结合蛋白（RBP）调节多种RNA种类，是寻找可操纵靶标以操纵和调整大脑中基因剪接反应的主要候选物。RBP优先识别靶向mRNA中的独特共有序列。同样，RBP通常包含多个RNA结合结构域（RBD）（每个具有唯一的共有序列），这暗示着可以开发药物来阻断单个功能域的可能性，从而提高了RBP靶向疗法的准确性。缺乏大多数RBP的经验表征，这是推进这一新兴治疗领域的主要障碍。关于RBP在大脑中的作用的数据很少，包括鉴定其独特的mRNA靶点，定义CNS损伤如何影响其水平以及阐明靶向哪些RBP（以及其中的各个域）以改善神经功能。这篇综述着眼于RBP肿瘤抑制物的最新技术RNA结合基序5（RBM5）。我们讨论了它在癌症中的强大的促死作用，这激发了我们对在大脑中进行研究的兴趣。我们回顾了最近的研究，显示中枢神经系统创伤后RBM5水平升高，并且其促进神经元死亡体外。最后，我们以在完整的大脑中鉴定出的第一套RBM5调控基因的最新报告作为结尾，并讨论这些发现如何提供与其在中枢神经系统中潜在功能密切相关的新线索，并对其在治疗中的实用性提出新的问题。减轻中枢神经系统损伤。