Conformational flexibility in RNA: The role of dihydrouridine
Conformational flexibility in RNA: The role of dihydrouridine
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DOI：
10.1093/nar/24.6.1073
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发表时间：
1996-03-15
影响因子：
14.9
通讯作者：
Davis, DR
中科院分区：
文献类型：
--
作者：
Dalluge, JJ;Hashizume, T;Davis, DR
为了进一步了解修饰后的核苷二氢吡啶在RNA中的结构作用，利用一维和二维质子核磁共振光谱分析了Dp和ApDpA的溶液构象，并与相关的含尿苷化合物进行了比较。结果表明，二氢吡啶显著破坏了与碱性叠合有序a型螺旋RNA相关的C3'-端糖构象的稳定性。平衡常数(K-eq = (C2的endo) / (C3的endo) C2的-endo-C3”endo在25摄氏度Dp互变现象,5 '末端ApDpA ApDpA和D为2.08,1.35和10.8分别稳定的C2的endo形式显示低温增强,表明C2的endo是热力学dihydrouridine青睐的构象,δH值表明,Dp C2的endo糖构象稳定1.5千卡/摩尔相比,这种效应在ApDpA寡核苷酸中的D中被放大，并传播到5‘端的A中，C2’端A的稳定性为5.3 kcal/mol, 5‘端A的稳定性为3.6 kcal/mol。因此，转录后形成的二氢吡啶代表了一种与核糖甲基化、2-硫代化或假嘌呤化相反的生物策略，所有这些都是通过稳定C3’端构象来增强区域稳定性的。二氢吡啶有效地促进了C2'-内切糖构象，允许更大的构象灵活性和RNA区域的动态运动，在那里三级相互作用和环形成必须同时进行。
In order to further understand the structural role of the modified nucleoside dihydrouridine in RNA the solution conformations of Dp and ApDpA were analyzed by one- and two-dimensional proton NMR spectroscopy and compared with those of the related uridine-containing compounds, The analyses indicate that dihydrouridine significantly destabilizes the C3'-endo sugar conformation associated with base stacked, ordered, A-type helical RNA, Equilibrium constants (K-eq = [C2'-endo]/[C3'-endo]) for C2'-endo-C3'-endo interconversion at 25 degrees C for Dp, the 5'-terminal A of ApDpA and D in ApDpA are 2.08, 1.35 and 10.8 respectively, Stabilization of the C2'-endo form was shown to be enhanced at low temperature, indicating that C2'-endo is the thermodynamically favored conformation for dihydrouridine, Delta H values show that for Dp the C2'-endo sugar conformation is stabilized by 1.5 kcal/mol compared with Up, This effect is amplified for D in the oligonucleotide ApDpA and propagated to the 5'-neighboring A, with stabilization of the C2'-endo form by 5.3 kcal/mol for D and 3.6 kcal/mol for the 5'-terminal A, Post-transcriptional formation of dihydrouridine therefore represents a biological strategy opposite in effect to ribose methylation, 2-thiolation or pseudouridylation, all of which enhance regional stability through stabilization of the C3'-endo conformer, Dihydrouridine effectively promotes the C2'-endo sugar conformation, allowing for greater conformational flexibility and dynamic motion in regions of RNA where tertiary interactions and loop formation must be simultaneously accomodated.