Institute for Molecular Biosciences, Goethe University, Frankfurt/M., Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany and Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University, Frankfurt/M., Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany.
Institute of Organic Chemistry, Centre for Molecular Biosciences (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Nucleic Acids Res. 2020 Jan 24;48(2):949-961. doi: 10.1093/nar/gkz1113.
RNA aptamers-artificially created RNAs with high affinity and selectivity for their target ligand generated from random sequence pools-are versatile tools in the fields of biotechnology and medicine. On a more fundamental level, they also further our general understanding of RNA-ligand interactions e. g. in regard to the relationship between structural complexity and ligand affinity and specificity, RNA structure and RNA folding. Detailed structural knowledge on a wide range of aptamer-ligand complexes is required to further our understanding of RNA-ligand interactions. Here, we present the atomic resolution structure of an RNA-aptamer binding to the fluorescent xanthene dye tetramethylrhodamine. The high resolution structure, solved by NMR-spectroscopy in solution, reveals binding features both common and different from the binding mode of other aptamers with affinity for ligands carrying planar aromatic ring systems such as the malachite green aptamer which binds to the tetramethylrhodamine related dye malachite green or the flavin mononucleotide aptamer.
RNA 适体——通过从随机序列库中生成对其靶配体具有高亲和力和选择性的人工 RNA——是生物技术和医学领域的多功能工具。在更基本的层面上,它们还进一步加深了我们对 RNA-配体相互作用的理解,例如在结构复杂性与配体亲和力和特异性、RNA 结构和 RNA 折叠之间的关系。为了进一步了解 RNA-配体相互作用,需要对广泛的适体-配体复合物进行详细的结构研究。在这里,我们展示了与荧光吖啶染料四甲基罗丹明结合的 RNA 适体的原子分辨率结构。该高分辨率结构通过溶液中的 NMR 光谱学确定,揭示了与其他与携带平面芳环系统的配体具有亲和力的适体的结合模式既有共同之处,也有不同之处,例如与四甲基罗丹明相关染料孔雀石绿结合的孔雀石绿适体或黄素单核苷酸适体。