Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Nucleic Acids Res. 2012 Sep;40(16):8111-8. doi: 10.1093/nar/gks426. Epub 2012 May 28.
Natural RNAs, especially tRNAs, are extensively modified to tailor structure and function diversities. Uracil is the most modified nucleobase among all natural nucleobases. Interestingly, >76% of uracil modifications are located on its 5-position. We have investigated the natural 5-methoxy (5-O-CH(3)) modification of uracil in the context of A-form oligonucleotide duplex. Our X-ray crystal structure indicates first a H-bond formation between the uracil 5-O-CH(3) and its 5'-phosphate. This novel H-bond is not observed when the oxygen of 5-O-CH(3) is replaced with a larger atom (selenium or sulfur). The 5-O-CH(3) modification does not cause significant structure and stability alterations. Moreover, our computational study is consistent with the experimental observation. The investigation on the uracil 5-position demonstrates the importance of this RNA modification at the atomic level. Our finding suggests a general interaction between the nucleobase and backbone and reveals a plausible function of the tRNA 5-O-CH(3) modification, which might potentially rigidify the local conformation and facilitates translation.
天然 RNA，尤其是 tRNA，广泛进行修饰以适应结构和功能的多样性。在所有天然碱基中，尿嘧啶是修饰最多的碱基。有趣的是，超过 76%的尿嘧啶修饰位于其 5 位。我们研究了 A 型寡核苷酸双链中天然的 5-甲氧基（5-O-CH(3)）修饰的尿嘧啶。我们的 X 射线晶体结构首先表明，尿嘧啶 5-O-CH(3)与其 5'-磷酸之间形成氢键。当 5-O-CH(3)中的氧被更大的原子（硒或硫）取代时，不会观察到这种新型氢键。5-O-CH(3)修饰不会引起明显的结构和稳定性改变。此外，我们的计算研究与实验观察一致。对尿嘧啶 5 位的研究表明，这种 RNA 修饰在原子水平上的重要性。我们的发现表明核碱基与骨架之间存在普遍的相互作用，并揭示了 tRNA 5-O-CH(3)修饰的潜在功能，这可能使局部构象更加稳定，并促进翻译。
