Centre de Recherche des Cordeliers, INSERM UMRS 1138, Sorbonne Université, Université Paris Cité, Equipe labellisée par la Ligue contre le Cancer, Institut universitaire de France, Paris, France.
Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.
Autophagy. 2023 Jul;19(7):1901-1915. doi: 10.1080/15548627.2023.2170071. Epub 2023 Feb 5.
Guanine-quadruplex structures (G4) are unusual nucleic acid conformations formed by guanine-rich DNA and RNA sequences and known to control gene expression mechanisms, from transcription to protein synthesis. So far, a number of molecules that recognize G4 have been developed for potential therapeutic applications in human pathologies, including cancer and infectious diseases. These molecules are called G4 ligands. When the biological effects of G4 ligands are studied, the analysis is often limited to nucleic acid targets. However, recent evidence indicates that G4 ligands may target other cellular components and compartments such as lysosomes and mitochondria. Here, we summarize our current knowledge of the regulation of lysosome by G4 ligands, underlying their potential functional impact on lysosome biology and autophagic flux, as well as on the transcriptional regulation of lysosomal genes. We outline the consequences of these effects on cell fate decisions and we systematically analyzed G4-prone sequences within the promoter of 435 lysosome-related genes. Finally, we propose some hypotheses about the mechanisms involved in the regulation of lysosomes by G4 ligands.
鸟嘌呤四链体结构（G4）是由富含鸟嘌呤的 DNA 和 RNA 序列形成的一种特殊核酸构象，已知其可控制从转录到蛋白质合成的基因表达机制。迄今为止，已经开发出许多能够识别 G4 的分子，这些分子可用于治疗人类疾病，包括癌症和传染病。这些分子被称为 G4 配体。当研究 G4 配体的生物学效应时，分析往往仅限于核酸靶标。然而，最近的证据表明，G4 配体可能靶向其他细胞成分和隔室，如溶酶体和线粒体。在这里，我们总结了目前对 G4 配体调节溶酶体的认识，包括它们对溶酶体生物学和自噬流的潜在功能影响，以及对溶酶体基因转录调控的影响。我们概述了这些效应对细胞命运决定的影响，并系统地分析了 435 个溶酶体相关基因启动子中易形成 G4 的序列。最后，我们提出了一些关于 G4 配体调节溶酶体的机制的假设。
