Institute of Bioorganic Chemistry, Polish Academy of Sciences, Z. Noskowskiego 12/14, 61-704 Poznań, Poland.
Saint Louis University, 3501 Laclede Ave., St. Louis, MO 63103-2010, United States.
Biophys Chem. 2019 Mar;246:35-39. doi: 10.1016/j.bpc.2018.12.006. Epub 2019 Jan 7.
Herein, we report comprehensive thermodynamic studies on 36 RNA/DNA duplexes designed as siRNA mimics to determine the energetic contribution of 3'T and 3'TT dangling ends. The thermodynamic effect induced by the presence of 3'T overhangs on the stability of RNA duplexes ranges from -0.28 to -0.92 kcal/mol and strongly depends on the type and orientation of the adjacent base pair. Further extension of the 3'-dangling end length, by a second T residue, results in additional stabilization of 0.14 to 0.21 kcal/mol. The results revealed that the thermodynamic contribution of 3'-dangling T and TT on RNA duplexes differs from the influence of 3'-dangling U and UU on RNA duplexes and 3'-dangling T and TT on DNA duplexes. This data suggests that using the contribution of 3'-dangling T values for RNA duplexes, instead of 3'-dangling T values for DNA duplexes or 3'-dangling U values for RNA duplexes, would improve the prediction of the stability of siRNA duplexes.
在这里,我们报告了 36 个 RNA/DNA 双链体的综合热力学研究,这些双链体被设计为 siRNA 模拟物,以确定 3'T 和 3'TT 悬垂末端的能量贡献。3'T 突出物存在对 RNA 双链体稳定性的热力学影响范围为-0.28 至-0.92 kcal/mol,并且强烈依赖于相邻碱基对的类型和取向。通过第二个 T 残基进一步延伸 3'-悬垂端长度,可额外稳定 0.14 至 0.21 kcal/mol。结果表明,3'-悬垂 T 和 TT 对 RNA 双链体的热力学贡献与 3'-悬垂 U 和 UU 对 RNA 双链体以及 3'-悬垂 T 和 TT 对 DNA 双链体的影响不同。这些数据表明,使用 3'-悬垂 T 值来预测 siRNA 双链体的稳定性,而不是使用 DNA 双链体的 3'-悬垂 T 值或 RNA 双链体的 3'-悬垂 U 值,将提高 siRNA 双链体稳定性的预测。