Ribozymes and riboswitches: modulation of RNA function by small molecules.
Ribozymes and riboswitches: modulation of RNA function by small molecules.
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DOI：
10.1021/bi1012645
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发表时间：
2010-11-02
期刊：
影响因子：
2.9
通讯作者：
Ferre-D'Amare, Adrian R.
中科院分区：
文献类型：
--
作者：
Zhang, Jinwei;Lau, Matthew W.;Ferre-D'Amare, Adrian R.
不同的小分子与作为底物和辅因子的催化RNA（核酶）相互作用，并且它们的细胞内浓度由调节转录、剪接、翻译或RNA稳定性的基因调节mRNA结构域（核糖开关）感测。虽然识别机制因RNA而异，但结构分析揭示了由RNA的固有特性引起的重复策略，例如碱基配对和与共轭杂环的堆叠，以及阴离子官能团的阳离子依赖性识别。这些研究还表明，在第一近似中，配体诱导的RNA重组的大小与核糖开关或核酶的复杂性成反比。这些小分子结合诱导的RNA变化如何导致基因表达的改变还不太清楚。虽然不同的核糖开关已被提出是在动力学或热力学控制下，引起小分子识别下游的RNA的调控后果的生化和结构机制大多仍有待阐明。
Diverse small molecules interact with catalytic RNAs (ribozymes) as substrates and cofactors, and their intracellular concentrations are sensed by gene-regulatory mRNA domains (riboswitches) that modulate transcription, splicing, translation, or RNA stability. Although recognition mechanisms vary from RNA to RNA, structural analyses reveal recurring strategies that arise from the intrinsic properties of RNA such as base pairing and stacking with conjugated heterocycles, and cation-dependent recognition of anionic functional groups. These studies also suggest that, to a first approximation, the magnitude of ligand-induced reorganization of an RNA is inversely proportional to the complexity of the riboswitch or ribozyme. How these small molecule binding-induced changes in RNA lead to alteration in gene expression is less well understood. While different riboswitches have been proposed to be under either kinetic or thermodynamic control, the biochemical and structural mechanisms that give rise to regulatory consequences downstream of small molecule recognition by RNAs mostly remain to be elucidated.
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