核開關(guān)是一個(gè)mRNA 內(nèi)的明確序列(適體),它們與一個(gè)配體(如一種代謝物)相結(jié)合,,其結(jié)合方式會改變該mRNA的結(jié)構(gòu),,影響該mRNA的表達(dá)。人們一直認(rèn)為,,核開關(guān)只有兩個(gè)狀態(tài):開或關(guān),。一項(xiàng)新的NMR研究表明,這種觀點(diǎn)太簡單化,。利用在存在于具有各種不同溫度的環(huán)境中的生物體內(nèi)所發(fā)現(xiàn)的一種核開關(guān),,Harald Schwalbe及其同事發(fā)現(xiàn),這種能感應(yīng)腺嘌呤,、由人類病原體Vibrio vulnificus的add基因編碼的核開關(guān)能存在于三種狀態(tài):開,、關(guān)和第三個(gè)位置,后者通過同時(shí)監(jiān)測溫度和配體濃度可對表達(dá)進(jìn)行更嚴(yán)格的控制,。(生物谷Bioon.com)
生物谷推薦英文摘要:
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.