Carlson Coby B, Stephens Olen M, Beal Peter A
University of Utah, Department of Chemistry, 315 South 1400 East, Room 2020, Salt Lake City, UT 84112, USA.
Biopolymers. 2003 Sep;70(1):86-102. doi: 10.1002/bip.10413.
Molecular recognition of double-stranded RNA (dsRNA) is a key event for numerous biological pathways including the trafficking, editing, and maturation of cellular RNA, the interferon antiviral response, and RNA interference. Over the past several years, our laboratory has studied proteins and small molecules that bind dsRNA with the goal of understanding and controlling the binding selectivity. In this review, we discuss members of the dsRBM class of proteins that bind dsRNA. The dsRBM is an approximately 70 amino acid sequence motif found in a variety of dsRNA-binding proteins. Recent results have led to a new appreciation of the ability of these proteins to bind selectivity to certain sites on dsRNA. This property is discussed in light of the RNA selectivity observed in the function of two proteins that contain dsRBMs, the RNA-dependent protein kinase (PKR) and an adenosine deaminase that acts on dsRNA (ADAR2). In addition, we introduce peptide-acridine conjugates (PACs), small molecules designed to control dsRBM-RNA interactions. These intercalating molecules bear variable peptide appendages at opposite edges of an acridine heterocycle. This design imparts the potential to exploit differences in groove characteristics and/or base-pair dynamics at binding sites to achieve selective binding.
双链RNA（dsRNA）的分子识别是众多生物途径中的关键事件，这些途径包括细胞RNA的运输、编辑和成熟、干扰素抗病毒反应以及RNA干扰。在过去几年中，我们实验室研究了与dsRNA结合的蛋白质和小分子，目的是理解和控制结合选择性。在这篇综述中，我们讨论了与dsRNA结合的dsRBM类蛋白质成员。dsRBM是在多种dsRNA结合蛋白中发现的一个约70个氨基酸的序列基序。最近的研究结果使人们对这些蛋白质选择性结合dsRNA特定位点的能力有了新的认识。结合含有dsRBM的两种蛋白质——RNA依赖性蛋白激酶（PKR）和作用于dsRNA的腺苷脱氨酶（ADAR2）——的功能中观察到的RNA选择性，对这一特性进行了讨论。此外，我们还介绍了肽-吖啶缀合物（PACs），即旨在控制dsRBM-RNA相互作用的小分子。这些嵌入分子在吖啶杂环的相对边缘带有可变的肽附属物。这种设计赋予了利用结合位点处凹槽特征和/或碱基对动态差异来实现选择性结合的潜力。
