环二鸟苷单磷酸核糖开关的结构与功能

Structure and function of c-di-GMP riboswitches

摘要:

环二鸟苷单磷酸 (c-di-GMP) 是细菌中广泛存在的一类核苷类第二信使分子，能够调控细菌的生物被膜形成、运动性、黏附、毒力以及胞外多糖的产生等众多生理活动。核糖开关是mRNA 5′-非翻译区(5′-Untranslational region, 5′-UTR) 的一段RNA序列，包含可以识别并结合配体的保守序列——适配体区(Aptamer domain, AD)，以及结构多变、可以调控下游编码基因的表达平台区 (Expression platform, EP)。当代谢物分子浓度比较高时，其与适配体区结合，引起下游的表达平台区发生构象变化，进而实现对下游基因的调节。目前已发现c-di-GMP-Ⅰ和c-di-GMP-Ⅱ两类c-di-GMP的核糖开关。它们通过特异性地结合c-di-GMP，调控种类繁多的下游基因的表达。c-di-GMP-I核糖开关分布广泛，尤其在厚壁菌门 (Firmicutes) 和变形菌门 (Proteobacteria) 的细菌中最为丰富。c-di-GMP-Ⅱ核糖开关具备变构核酶的功能，结合c-di-GMP后在其非典型剪切位点处发生结构变化，调节下游基因表达。文中围绕c-di-GMP核糖开关的发现、功能、分类以及下游调控基因的功能进行综述与分析。

Abstract:

Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous nucleotide second messenger present in a wide variety of bacteria. It regulates many important bacterial physiological functions such as biofilm formation, motility, adhesion, virulence and extracellular polysaccharide synthesis. It binds with many different proteins or RNA receptors, one of which is called riboswitch that is usually located at the 5′-untranslational region (5′-UTR) in some mRNA. Riboswitch usually comprises a specific ligand-binding (sensor) domain (named aptamer domain, AD), as well as a variable domain, termed expression platform (EP), to regulate expression of downstream coding sequences. When a specific metabolite concentration exceeds its threshold level, it will bind to its cognate riboswitch receptor to induce a conformational change of 5′-UTR, leading to modulation of downstream gene expression. Two classes of c-di-GMP-binding riboswitches (c-di-GMP-Ⅰ and c-di-GMP-Ⅱ) have been discovered that bind with this second messenger with high affinity to regulate diverse downstream genes, underscoring the importance of this unique RNA receptor in this pathway. Class Ⅰ c-di-GMP riboswitches are present in a wide variety of bacteria, and are most common in the phyla Firmicutes and Proteobacteria, while class Ⅱ c-di-GMP riboswitches typically function as allosteric ribozymes, binding to c-di-GMP to induce folding changes at atypical splicing site junctions to modulate downstream gene expression. This review introduces the discovery, classification, function, and also the affected downstream genes of c-di-GMP riboswitches.