Department of Biochemistry, University of Washington, Seattle, WA 98195-1700, USA.
FEBS J. 2013 Aug;280(16):3734-54. doi: 10.1111/febs.12375. Epub 2013 Jul 5.
RNA-binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA-binding proteins has shown that RNA-binding domains may be combined with various effector or functional domains to regulate the metabolism of targeted RNAs. Designer RNA-binding proteins with tailored sequence specificity will provide valuable tools for biochemical research as well as potential therapeutic applications. In this review, we discuss the suitability of various RNA-binding domains for engineering RNA-binding specificity, based on the structural basis for their recognition. We also compare various protein engineering and design methods applied to RNA-binding proteins, and discuss future applications of these proteins.
RNA 结合蛋白在基因表达调控中发挥着重要作用。许多 RNA 结合蛋白具有模块化结构,并以各种排列方式组合相对较少的常见结构域,以识别 RNA 序列和/或结构。最近在工程 PUF 类 RNA 结合蛋白特异性方面的进展表明,RNA 结合结构域可以与各种效应器或功能结构域结合,以调节靶向 RNA 的代谢。具有定制序列特异性的设计 RNA 结合蛋白将为生化研究以及潜在的治疗应用提供有价值的工具。在这篇综述中,我们将根据其识别的结构基础,讨论各种 RNA 结合结构域用于工程 RNA 结合特异性的适用性。我们还比较了应用于 RNA 结合蛋白的各种蛋白质工程和设计方法,并讨论了这些蛋白质的未来应用。