配体响应性RNA开关中结构虽有差异但功能保守。
Functional conservation despite structural divergence in ligand-responsive RNA switches.
作者信息
Boerneke Mark A, Dibrov Sergey M, Gu Jing, Wyles David L, Hermann Thomas
机构信息
Department of Chemistry and Biochemistry.
Division of Infectious Diseases, Department of Medicine, and.
出版信息
Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):15952-7. doi: 10.1073/pnas.1414678111. Epub 2014 Oct 27.
Abstract
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.
摘要
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。
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本文引用的文献
1
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Nat Struct Mol Biol. 2014 Aug;21(8):721-7. doi: 10.1038/nsmb.2859. Epub 2014 Jul 27.
2
Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.丙型肝炎病毒翻译抑制剂靶向内部核糖体进入位点。
J Med Chem. 2014 Mar 13;57(5):1694-707. doi: 10.1021/jm401312n. Epub 2013 Nov 5.
3
Screening for inhibitors of the hepatitis C virus internal ribosome entry site RNA.筛选丙型肝炎病毒内部核糖体进入位点 RNA 的抑制剂。
Bioorg Med Chem. 2013 Oct 15;21(20):6139-44. doi: 10.1016/j.bmc.2013.03.054. Epub 2013 Apr 2.
4
HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.HCV IRES 操纵核糖体以促进从翻译起始向延伸的转变。
Nat Struct Mol Biol. 2013 Feb;20(2):150-8. doi: 10.1038/nsmb.2465. Epub 2012 Dec 23.
5
Targeting a regulatory element in human thymidylate synthase mRNA.靶向人胸苷酸合成酶 mRNA 的调控元件。
Chembiochem. 2012 Dec 21;13(18):2738-44. doi: 10.1002/cbic.201200603. Epub 2012 Nov 9.
6
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7
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Structure. 2011 Oct 12;19(10):1456-66. doi: 10.1016/j.str.2011.08.002.
10
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Nucleic Acids Res. 2011 Oct;39(19):8628-37. doi: 10.1093/nar/gkr452. Epub 2011 Jul 7.
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