HIV-1 基因组 RNA U3 区形成稳定的四联体-发夹结构。
HIV-1 genomic RNA U3 region forms a stable quadruplex-hairpin structure.
机构信息
Department of Chemistry and Biochemistry, Center for Retroviral Research and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
Department of Chemistry and Biochemistry, Center for Retroviral Research and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
出版信息
Biophys Chem. 2021 May;272:106567. doi: 10.1016/j.bpc.2021.106567. Epub 2021 Mar 8.
The U3 promoter region of the HIV-1 long terminal repeat (LTR) has previously been shown to fold into a series of dynamic G-quadruplex structures. Among the G-quadruplexes identified in the LTR sequence, LTR-III was shown to be the most stable in vitro. NMR studies of this 28-nucleotide (nt) DNA revealed a unique quadruplex-hairpin structure. Whether the hairpin forms in RNA element is unknown and the role of the hairpin in the structure and stability of quadruplexes has not been characterized. Here, we used optical and thermodynamic studies to address these questions. The wild-type LTR-III RNA formed a monomolecular quadruplex with a parallel topology using only propeller loops, including the hairpin loop element. By comparison to the WT and variant RNAs, LTR-III DNA structures were more heterogeneous and less stable. Increased stability of the RNA suggests that the RNA quadruplex-hairpin structure may be a more attractive therapeutic target than the analogous DNA element.
HIV-1 长末端重复序列（LTR）的 U3 启动子区域先前已被证明可折叠成一系列动态 G-四链体结构。在 LTR 序列中鉴定出的 G-四链体中，LTR-III 在体外显示出最稳定。对该 28 个核苷酸（nt）DNA 的 NMR 研究揭示了一种独特的四链体-发夹结构。发夹是否在 RNA 元件中形成尚不清楚，并且发夹在四链体的结构和稳定性中的作用尚未得到表征。在这里，我们使用光学和热力学研究来解决这些问题。野生型 LTR-III RNA 仅使用推进器环，包括发夹环元件，形成具有平行拓扑的单分子四链体。与 WT 和变体 RNA 相比，LTR-III DNA 结构更加异质且稳定性更低。RNA 稳定性的增加表明，RNA 四链体-发夹结构可能比类似的 DNA 元件更具吸引力的治疗靶标。
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