MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Mol Cell Neurosci. 2013 Sep;56:429-35. doi: 10.1016/j.mcn.2013.04.002. Epub 2013 Apr 10.
The fate of an mRNA is largely determined by its interactions with RNA binding proteins (RBPs). Post-transcriptional processing, RNA stability, localisation and translation are some of the events regulated by the plethora of RBPs present within cells. Mutations in various RBPs cause several diseases of the central nervous system, including frontotemporal lobar degeneration, amyotrophic lateral sclerosis and fragile X syndrome. Here we review the studies that integrated UV-induced cross-linked immunoprecipitation (CLIP) with other genome-wide methods to comprehensively characterise the function of diverse RBPs in the brain. We discuss the technical challenges of these studies and review the strategies that can be used to reliably identify the RNAs bound and regulated by an RBP. We conclude by highlighting how CLIP and related techniques have been instrumental in addressing the role of RBPs in neurologic diseases. This article is part of a Special Issue entitled: RNA and splicing regulation in neurodegeneration.
mRNA 的命运在很大程度上取决于其与 RNA 结合蛋白 (RBP) 的相互作用。转录后加工、RNA 稳定性、定位和翻译是由细胞内存在的大量 RBP 调节的一些事件。各种 RBP 的突变导致中枢神经系统的多种疾病，包括额颞叶痴呆、肌萎缩侧索硬化症和脆性 X 综合征。在这里，我们回顾了将紫外线诱导的交联免疫沉淀 (CLIP) 与其他全基因组方法相结合的研究，以全面描述大脑中不同 RBP 的功能。我们讨论了这些研究的技术挑战，并回顾了可用于可靠识别 RBP 结合和调节的 RNA 的策略。最后，我们强调了 CLIP 及相关技术在解决 RBP 在神经疾病中的作用方面的重要性。本文是题为“神经退行性疾病中的 RNA 和剪接调控”特刊的一部分。
