Deep Auroni, Bhat Anjali, Perumal Vivekanandan, Kumar Saran
Kusuma School of Biological Sciences, Indian Institute of Technology, Delhi 110016, India.
Mol Ther Nucleic Acids. 2025 Feb 1;36(1):102474. doi: 10.1016/j.omtn.2025.102474. eCollection 2025 Mar 11.
i-Motifs, cytosine-tetrads, or C-quadruplexes are intercalated structures formed by base pairing between cytosine and protonated cytosine. These structures demonstrate increased stability in acidic environments due to the presence of the latter cytosinium group (i.e., the protonated cytosine). Research has shown that i-motifs are typically disrupted or destabilized at physiological pH levels (7.0-7.4), which makes their potential formation in the nucleus and their biological relevance uncertain. However, in 2018, it was demonstrated that i-motifs exist within the nucleus under physiological conditions, with various intracellular factors contributing to their stability. Identification of i-motifs in the nucleus and their association with gene promoters-particularly with those of proto-oncogenes-has generated significant interest in their potential regulatory functions. Additionally, recent studies suggest that i-motifs may function as switches for gene expression, influencing gene regulation through their folding and stabilization or unfolding and destabilization. This review aims to delve into these mechanisms to improve our understanding of the physiological significance of i-motifs.
i-基序、胞嘧啶四联体或C-四链体是由胞嘧啶与质子化胞嘧啶之间的碱基配对形成的插入结构。由于存在后者的胞嘧啶鎓基团（即质子化胞嘧啶），这些结构在酸性环境中表现出更高的稳定性。研究表明，i-基序通常在生理pH水平（7.0 - 7.4）下被破坏或不稳定，这使得它们在细胞核中的潜在形成及其生物学相关性变得不确定。然而，在2018年，有研究证明i-基序在生理条件下存在于细胞核中，各种细胞内因子有助于其稳定性。在细胞核中鉴定出i-基序及其与基因启动子的关联——特别是与原癌基因启动子的关联——引发了人们对其潜在调控功能的极大兴趣。此外，最近的研究表明，i-基序可能作为基因表达的开关，通过其折叠和稳定或展开和不稳定来影响基因调控。这篇综述旨在深入探讨这些机制，以增进我们对i-基序生理意义的理解。
