Chemistry Department of Lomonosov Moscow State University, Moscow, Russia.
Chemistry Department of Lomonosov Moscow State University, Moscow, Russia; Enikolopov Institute of Synthetic Polymeric Materials of Russian Academy of Sciences, Moscow, Russia.
Biophys Chem. 2025 Jan;316:107350. doi: 10.1016/j.bpc.2024.107350. Epub 2024 Nov 12.
Non-canonical nucleic acid structures possess an ability to interact selectively with proteins, thereby exerting influence over various intracellular processes. Numerous studies indicate that genomic G-quadruplexes and i-motifs are involved in the regulation of transcription. These structures are formed temporarily during the unwinding of the DNA double helix; and their direct determination is a rather difficult task. In addition, i-motif folding is pH-dependent, with most i-motifs having low stability at neutral pH. However, some genomic i-motifs with long cytosine repeats were shown to be stable at pH 7.3, suggesting their functionality within the nucleus. Here we studied pH-dependent behavior of a model i-motif with flanking sequences that forms a duplex motif. Kinetic studies on bimodular structures with cytosine residues replaced with an environment-sensitive fluorescent label reveal the stabilization of the i-motif structure near the i-motif-duplex junction. These results highlight the importance of the natural environment of i-motifs for the correct assessment of their stability.
非经典核酸结构具有与蛋白质选择性相互作用的能力，从而对各种细胞内过程产生影响。大量研究表明，基因组 G-四链体和 i- 基序参与转录的调控。这些结构是在 DNA 双螺旋解链过程中临时形成的；直接确定它们的结构是一项相当困难的任务。此外，i- 基序折叠依赖于 pH 值，大多数 i- 基序在中性 pH 值下稳定性较低。然而，一些具有长胞嘧啶重复序列的基因组 i- 基序在 pH 7.3 下表现出稳定，表明它们在核内具有功能。在这里，我们研究了侧翼序列形成双链基序的模型 i- 基序的 pH 依赖性行为。用环境敏感荧光标记物替换带有胞嘧啶残基的双模块结构的动力学研究揭示了 i- 基序结构在 i- 基序-双链基序连接处的稳定化。这些结果强调了 i- 基序的自然环境对于正确评估其稳定性的重要性。
