Boerneke Mark A, Dibrov Sergey M, Gu Jing, Wyles David L, Hermann Thomas
Department of Chemistry and Biochemistry.
Division of Infectious Diseases, Department of Medicine, and.
Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):15952-7. doi: 10.1073/pnas.1414678111. Epub 2014 Oct 27.
An internal ribosome entry site (IRES) initiates protein synthesis in RNA viruses, including the hepatitis C virus (HCV). We have discovered ligand-responsive conformational switches in viral IRES elements. Modular RNA motifs of greatly distinct sequence and local secondary structure have been found to serve as functionally conserved switches involved in viral IRES-driven translation and may be captured by identical cognate ligands. The RNA motifs described here constitute a new paradigm for ligand-captured switches that differ from metabolite-sensing riboswitches with regard to their small size, as well as the intrinsic stability and structural definition of the constitutive conformational states. These viral RNA modules represent the simplest form of ligand-responsive mechanical switches in nucleic acids.
内部核糖体进入位点（IRES）可启动包括丙型肝炎病毒（HCV）在内的RNA病毒中的蛋白质合成。我们在病毒IRES元件中发现了配体响应性构象开关。已发现序列和局部二级结构截然不同的模块化RNA基序可作为参与病毒IRES驱动翻译的功能保守开关，并可能被相同的同源配体捕获。本文所述的RNA基序构成了一种配体捕获开关的新范式，其在大小、组成构象状态的内在稳定性和结构定义方面与代谢物感应核糖开关不同。这些病毒RNA模块代表了核酸中配体响应性机械开关的最简单形式。
