核开关是一个mRNA 内的明确序列(适体),它们与一个配体(如一种代谢物)相结合,其结合方式会改变该mRNA的结构,影响该mRNA的表达。人们一直认为,核开关只有两个状态:开或关。一项新的NMR研究表明,这种观点太简单化。利用在存在于具有各种不同温度的环境中的生物体内所发现的一种核开关,Harald Schwalbe及其同事发现,这种能感应腺嘌呤、由人类病原体Vibrio vulnificus的add基因编码的核开关能存在于三种状态:开、关和第三个位置,后者通过同时监测温度和配体浓度可对表达进行更严格的控制。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi: 10.1038/nature12378
Three-state mechanism couples ligand and temperature sensing in riboswitches
Anke Reining, Senada Nozinovic, Kai Schlepckow, Florian Buhr, Boris Fürtig & Harald Schwalbe
Riboswitches are cis-acting gene-regulatory RNA elements that can function at the level of transcription, translation and RNA cleavage. The commonly accepted molecular mechanism for riboswitch function proposes a ligand-dependent conformational switch between two mutually exclusive states. According to this mechanism, ligand binding to an aptamer domain induces an allosteric conformational switch of an expression platform, leading to activation or repression of ligand-related gene expression. However, many riboswitch properties cannot be explained by a pure two-state mechanism. Here we show that the regulation mechanism of the adenine-sensing riboswitch, encoded by the add gene on chromosome II of the human Gram-negative pathogenic bacterium Vibrio vulnificus, is notably different from a two-state switch mechanism in that it involves three distinct stable conformations. We characterized the temperature and Mg2+ dependence of the population ratios of the three conformations and the kinetics of their interconversion at nucleotide resolution. The observed temperature dependence of a pre-equilibrium involving two structurally distinct ligand-free conformations of the add riboswitch conferred efficient regulation over a physiologically relevant temperature range. Such robust switching is a key requirement for gene regulation in bacteria that have to adapt to environments with varying temperatures. The translational adenine-sensing riboswitch represents the first example, to our knowledge, of a temperature-compensated regulatory RNA element.