Department Medical Research Central, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Clinical Biobank, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
J Mol Med (Berl). 2023 Jun;101(6):621-635. doi: 10.1007/s00109-023-02314-7. Epub 2023 Apr 18.
Non-coding RNAs (ncRNAs) are significant regulators of gene expression in a wide range of biological processes, such as transcription, RNA maturation, or translation. ncRNAs interplay with proteins or other RNAs through not only classical sequence-based mechanisms but also unique higher-order structures such as RNA G-quadruplexes (rG4s). rG4s are predictably formed in guanine-rich sequences and are closely related to various human diseases, such as tumors, neurodegenerative diseases, and infections. This review focuses on the vital role of rG4s in ncRNAs, particularly lncRNAs and miRNAs. We outline the dynamic balance between rG4s and RNA stem-loop/hairpin structures and the interplay between ncRNAs and interactors, thereby modulating gene expression and disease progression. A complete understanding of the biological regulatory role and mechanism of rG4s in ncRNAs affirms the critical importance of folding into the appropriate three-dimensional structure in maintaining or modulating the functions of ncRNAs. It makes them novel therapeutic targets for adjusting potential-G4-containing-ncRNAs-associated diseases.
非编码 RNA(ncRNA)是广泛的生物学过程中基因表达的重要调控因子,例如转录、RNA 成熟或翻译。ncRNA 通过不仅基于经典序列的机制,而且通过独特的高级结构(如 RNA G-四链体(rG4))与蛋白质或其他 RNA 相互作用。rG4 在富含鸟嘌呤的序列中可预测形成,与各种人类疾病密切相关,例如肿瘤、神经退行性疾病和感染。本综述重点介绍 rG4 在 ncRNA 中的重要作用,特别是长链非编码 RNA(lncRNA)和 microRNA(miRNA)。我们概述了 rG4 与 RNA 茎环/发夹结构之间的动态平衡以及 ncRNA 与相互作用物之间的相互作用,从而调节基因表达和疾病进展。对 rG4 在 ncRNA 中的生物学调节作用和机制的全面理解证实了折叠成适当的三维结构对于维持或调节 ncRNA 功能的至关重要性。这使得它们成为调节潜在富含 G4 的 ncRNA 相关疾病的新型治疗靶标。