Wang Rui, Vangaveti Sweta, Ranganathan Srivathsan V, Basanta-Sanchez Maria, Haruehanroengra Phensinee, Chen Alan, Sheng Jia
Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
Nucleic Acids Res. 2016 Jul 27;44(13):6036-45. doi: 10.1093/nar/gkw544. Epub 2016 Jun 15.
Natural RNAs utilize extensive chemical modifications to diversify their structures and functions. 2-Thiouridine geranylation is a special hydrophobic tRNA modification that has been discovered very recently in several bacteria, such as Escherichia coli, Enterobacter aerogenes, Pseudomonas aeruginosa and Salmonella Typhimurium The geranylated residues are located in the first anticodon position of tRNAs specific for lysine, glutamine and glutamic acid. This big hydrophobic terpene functional group affects the codon recognition patterns and reduces frameshifting errors during translation. We aimed to systematically study the structure, function and biosynthesis mechanism of this geranylation pathway, as well as answer the question of why nature uses such a hydrophobic modification in hydrophilic RNA systems. Recently, we have synthesized the deoxy-analog of S-geranyluridine and showed the geranylated T-G pair is much stronger than the geranylated T-A pair and other mismatched pairs in the B-form DNA duplex context, which is consistent with the observation that the geranylated tRNA(Glu) UUC recognizes GAG more efficiently than GAA. In this manuscript we report the synthesis and base pairing specificity studies of geranylated RNA oligos. We also report extensive molecular simulation studies to explore the structural features of the geranyl group in the context of A-form RNA and its effect on codon-anticodon interaction during ribosome binding.
天然RNA利用广泛的化学修饰来使其结构和功能多样化。2-硫代尿苷香叶基化是一种特殊的疏水性tRNA修饰，最近在几种细菌中被发现，如大肠杆菌、产气肠杆菌、铜绿假单胞菌和鼠伤寒沙门氏菌。香叶基化的残基位于赖氨酸、谷氨酰胺和谷氨酸特异性tRNA的第一个反密码子位置。这个大的疏水性萜烯官能团影响密码子识别模式，并减少翻译过程中的移码错误。我们旨在系统地研究这种香叶基化途径的结构、功能和生物合成机制，以及回答为什么自然界在亲水性RNA系统中使用这种疏水性修饰的问题。最近，我们合成了S-香叶基尿苷的脱氧类似物，并表明在B型DNA双链体环境中，香叶基化的T-G对比香叶基化的T-A对和其他错配对比更强，这与香叶基化的tRNA(Glu) UUC比GAA更有效地识别GAG的观察结果一致。在本论文中，我们报告了香叶基化RNA寡聚物的合成和碱基配对特异性研究。我们还报告了广泛的分子模拟研究，以探索在A型RNA环境中香叶基的结构特征及其对核糖体结合过程中密码子-反密码子相互作用的影响。
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