Division of Materials Science and Chemistry, Faculty of Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan.
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Nucleic Acids Res. 2022 Aug 12;50(14):8143-8153. doi: 10.1093/nar/gkac580.
Tandem repeats of guanine-rich sequences in RNA often form thermodynamically stable four-stranded RNA structures. Such RNA G-quadruplexes have long been considered to be linked to essential biological processes, yet their physiological significance in cells remains unclear. Here, we report a approach that permits the detection of RNA G-quadruplex structures that modulate protein translation in mammalian cells. The approach combines antibody arrays and RGB-1, a small molecule that selectively stabilizes RNA G-quadruplex structures. Analysis of the protein and mRNA products of 84 cancer-related human genes identified Nectin-4 and CapG as G-quadruplex-controlled genes whose mRNAs harbor non-canonical G-quadruplex structures on their 5'UTR region. Further investigations revealed that the RNA G-quadruplex of CapG exhibits a structural polymorphism, suggesting a possible mechanism that ensures the translation repression in a KCl concentration range of 25-100 mM. The approach described in the present study sets the stage for further discoveries of RNA G-quadruplexes.
RNA 中富含鸟嘌呤的序列串联重复通常形成热力学稳定的四链 RNA 结构。这种 RNA G-四链体长期以来被认为与重要的生物过程有关，但它们在细胞中的生理意义仍不清楚。在这里，我们报告了一种可以检测调节哺乳动物细胞中蛋白质翻译的 RNA G-四链体结构的方法。该方法结合了抗体阵列和 RGB-1，一种选择性稳定 RNA G-四链体结构的小分子。对 84 个人类癌症相关基因的蛋白质和 mRNA 产物进行分析，确定 Nectin-4 和 CapG 为 G-四链体控制基因，其 mRNA 在 5'UTR 区域具有非典型的 G-四链体结构。进一步的研究表明，CapG 的 RNA G-四链体表现出结构多态性，这表明一种可能的机制，确保了在 25-100mM 的 KCl 浓度范围内的翻译抑制。本研究中描述的方法为进一步发现 RNA G-四链体奠定了基础。
