当前位置: X-MOL 学术Sci. Rep. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Computational and NMR studies of RNA duplexes with an internal pseudouridine-adenosine base pair.
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-07 , DOI: 10.1038/s41598-019-52637-0
Indrajit Deb 1, 2, 3 , Łukasz Popenda 4 , Joanna Sarzyńska 1 , Magdalena Małgowska 1 , Ansuman Lahiri 2 , Zofia Gdaniec 1 , Ryszard Kierzek 1
Affiliation  

Pseudouridine (Ψ) is the most common chemical modification present in RNA. In general, Ψ increases the thermodynamic stability of RNA. However, the degree of stabilization depends on the sequence and structural context. To explain experimentally observed sequence dependence of the effect of Ψ on the thermodynamic stability of RNA duplexes, we investigated the structure, dynamics and hydration of RNA duplexes with an internal Ψ-A base pair in different nearest-neighbor sequence contexts. The structures of two RNA duplexes containing 5'-GΨC/3'-CAG and 5'-CΨG/3'-GAC motifs were determined using NMR spectroscopy. To gain insight into the effect of Ψ on duplex dynamics and hydration, we performed molecular dynamics (MD) simulations of RNA duplexes with 5'-GΨC/3'-CAG, 5'-CΨG/3'-GAC, 5'-AΨU/3'-UAA and 5'-UΨA/3'-AAU motifs and their unmodified counterparts. Our results showed a subtle impact from Ψ modification on the structure and dynamics of the RNA duplexes studied. The MD simulations confirmed the change in hydration pattern when U is replaced with Ψ. Quantum chemical calculations showed that the replacement of U with Ψ affected the intrinsic stacking energies at the base pair steps depending on the sequence context. The calculated intrinsic stacking energies help to explain the experimentally observed sequence dependent changes in the duplex stability from Ψ modification.

中文翻译:

具有内部假尿苷-腺苷碱基对的RNA双链体的计算和NMR研究。

假性尿苷(Ψ)是RNA中最常见的化学修饰。通常,Ψ可增加RNA的热力学稳定性。但是,稳定度取决于序列和结构背景。为了解释实验观察到的Ψ对RNA双链体热力学稳定性的影响的序列依赖性,我们研究了在不同的最近邻序列环境中带有内部Ψ-A碱基对的RNA双链体的结构,动力学和水合作用。使用NMR光谱法确定了两个含有5'-GΨC/ 3'-CAG和5'-CΨG/ 3'-GAC基序的RNA双链体的结构。为了深入了解of对双链体动力学和水合的影响,我们使用5'-GΨC/ 3'-CAG,5'-CΨG/ 3'-GAC,5'-AΨU对RNA双链体进行了分子动力学(MD)模拟/ 3'-UAA和5' -UΨA/ 3'-AAU图案及其未修饰的对应物。我们的结果表明,from修饰对所研究的RNA双链体的结构和动力学具有微妙的影响。MD模拟结果证实了用U代替U时水化模式的变化。量子化学计算表明,用the取代U会影响碱基对步长的固有堆积能,具体取决于序列的上下文。计算出的固有堆积能有助于解释由Ψ修饰引起的双链体稳定性的实验观察到的序列依赖性变化。量子化学计算表明,用the取代U会影响碱基对步长的固有堆积能,具体取决于序列的上下文。计算出的固有堆积能有助于解释由Ψ修饰引起的双链体稳定性的实验观察到的序列依赖性变化。量子化学计算表明,用the取代U会影响碱基对步长的固有堆积能,具体取决于序列的上下文。计算出的固有堆积能有助于解释由Ψ修饰引起的双链体稳定性的实验观察到的序列依赖性变化。
更新日期:2019-11-07
down
wechat
bug