核开关(riboswitch)是Breaker等在2002年发现的一种全新的转录后调节机制.它可以通过小分子与mRNA结合来直接调控基因的表达,不需要任何蛋白质的参与.与常见的经由蛋白质的调控方式相比,riboswitch响应更迅速,对细胞内代谢物的变化更敏感.它的发现为RNA研究展示了新的领域. 目前在这个领域,既有基础研究,如riboswitch晶体结构解析、作用机制和动力学研究,又有前沿应用研究,如基于riboswitch的生物传感器和药物设计.Topp等通过设计riboswitch成功地改变了大肠杆菌的趋化性,这为合成生物学和人工生物网络的设计提供了新思路.目前对于riboswitch结构、机制及动力学的研究为基于riboswitch的合理药物设计奠定了基础,有望针对这一新的机制开发新一代抗菌药物.
Riboswitch is a novel type of posttranscriptional regulatory elements discovered by Breaker et al. in 2002. It can regulate gene expression by binding directly to small metabolites without the aid of protein molecules. Compared to normal protein-mediated regulation, riboswitch responds to metabolites more rapidly and sensitively. Its discovery opens a new world for RNA research. The recent advances in riboswitch researches were summarized, including crystal structure determination, mechanism and dynamics study, biosensor and antibacterial drug design. Topp et al. successfully reprogrammed E. coli to detect, follow, and precisely localize to a completely new chemical signal by using a synthetic riboswitch. This work provided new ideas for synthetic biology and artificial biology network. The advances in riboswitch 3D structure determination, reaction mechanism and dynamics provide useful information for rational drug design towards new generation of riboswitch-targeting antibacterials.
何珊,来鲁华.核开关结构、机制及应用新进展[J].生物化学与生物物理进展,2010,37(1):7-13
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