Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
RNA. 2010 Mar;16(3):598-609. doi: 10.1261/rna.1852310. Epub 2010 Jan 27.
Riboswitches are structured mRNA elements that regulate gene expression upon binding specific cellular metabolites. It is thought that the highly conserved metabolite-binding domains of riboswitches undergo conformational change upon binding their cognate ligands. To investigate the generality of such a mechanism, we employed small-angle X-ray scattering (SAXS). We probed the nature of the global metabolite-induced response of the metabolite-binding domains of four different riboswitches that bind, respectively, thiamine pyrophosphate (TPP), flavin mononucleotide (FMN), lysine, and S-adenosyl methionine (SAM). We find that each RNA is unique in its global structural response to metabolite. Whereas some RNAs exhibit distinct free and bound conformations, others are globally insensitive to the presence of metabolite. Thus, a global conformational change of the metabolite-binding domain is not a requirement for riboswitch function. It is possible that the range of behaviors observed by SAXS, rather than being a biophysical idiosyncrasy, reflects adaptation of riboswitches to the regulatory requirements of their individual genomic context.
Riboswitches 是一种结构型的 mRNA 元件，能够在结合特定的细胞代谢物后调节基因表达。人们认为，riboswitches 中高度保守的代谢物结合结构域在与它们的同源配体结合时会发生构象变化。为了研究这种机制的普遍性，我们采用了小角 X 射线散射（SAXS）技术。我们探测了四个不同的 riboswitches 的代谢物结合结构域在结合相应配体时，全局代谢物诱导响应的性质，这四个 riboswitches 分别结合硫胺素焦磷酸（TPP）、黄素单核苷酸（FMN）、赖氨酸和 S-腺苷甲硫氨酸（SAM）。我们发现，每个 RNA 在其对代谢物的全局结构响应方面都是独特的。虽然有些 RNA 表现出明显的自由和结合构象，但其他 RNA 对代谢物的存在则完全不敏感。因此，代谢物结合结构域的全局构象变化并不是 riboswitch 功能的必要条件。通过 SAXS 观察到的一系列行为，可能不是一种生物物理特性，而是反映了 riboswitches 对其各自基因组环境的调节要求的适应性。
