Liu Lutan, Takahashi Shuntaro, Ghosh Sarptarshi, Endoh Tamaki, Yoshinaga Naoto, Numata Keiji, Sugimoto Naoki
FIBER (Frontier Institute for Biomolecular Engineering Research), Konan University, Chuo-ku, Kobe, Japan.
FIRST (Graduate School of Frontiers of Innovative Research in Science and Technology), Konan University, Chuo-ku, Kobe, Japan.
Commun Chem. 2025 May 3;8(1):135. doi: 10.1038/s42004-025-01532-z.
Molecular crowding affects the stability of nucleic acids (DNA and RNA) and induces their non-canonical structures. As the level of molecular crowding varies spatio-temporally in cells, it would be beneficial to predict the behaviour of DNA and RNA structures depending on the local cellular environments. This has applications in human mitochondria, which possess an especially crowded condition. In this study, the predictability of guanine-quadruplex (G4) DNA formation in the environment specific to human mitochondria was investigated. In accordance with the stability of duplexes predicted by our nearest-neighbour parameters, the G-rich duplex stability was found to effectively decrease and G4 formation was induced in mitochondrion-like conditions compared to the nucleus-like conditions. Using a peptide-based mitochondrial targeting system, a G4 reporter assay performed in mitochondria indicated that G4 formation were more favoured in mitochondria more than in the nucleus. These findings provide insights useful for the prediction of the behaviour of nucleic acids in mitochondria.
分子拥挤效应会影响核酸（DNA和RNA）的稳定性并诱导其形成非规范结构。由于分子拥挤程度在细胞内随时间和空间变化，根据局部细胞环境预测DNA和RNA结构的行为将大有裨益。这在人类线粒体中具有应用价值，因为线粒体具有特别拥挤的环境。在本研究中，我们调查了在人类线粒体特有的环境中鸟嘌呤四链体（G4）DNA形成的可预测性。根据我们的近邻参数预测的双链稳定性，与类核条件相比，富含G的双链稳定性在类线粒体条件下有效降低，并诱导了G4的形成。使用基于肽的线粒体靶向系统，在线粒体中进行的G4报告基因检测表明，线粒体中G4的形成比细胞核中更受青睐。这些发现为预测线粒体中核酸的行为提供了有用的见解。
