Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
J Am Chem Soc. 2021 Jul 28;143(29):11036-11043. doi: 10.1021/jacs.1c03627. Epub 2021 Jul 16.
Biomolecular condensates comprised of specific proteins and nucleic acids are now recognized as one of the key organizing mechanisms in eukaryotic cells. However, the specific roles played by the nucleic acid secondary structure and sequence in biomolecular phase separation are still not clear. Here, utilizing giant membrane vesicles (GMVs) as a protocell model, we found that single-stranded DNA (ssDNA) with a parallel G-quadruplex structure could functionally cooperate with a G-quadruplex-binding protein to form speckle-like puncta inside the GMVs. The clustering behavior is dependent on the structural diversity of G-quadruplexes, and the reversible clustering behavior implicated a new pathway in dynamically regulating the formation of biomolecular condensates. This finding represents a potential link between G-quadruplex-binding proteins and the resulting G-quadruplex-mediated biomolecular phase separation, which would gain insight into a wide range of biological processes associated with nucleic acid-modulated phase separation inside living cells.
生物分子凝聚体由特定的蛋白质和核酸组成，现在被认为是真核细胞的主要组织机制之一。然而，核酸二级结构和序列在生物分子相分离中所起的具体作用仍不清楚。在这里，我们利用巨膜囊泡（GMVs）作为原细胞模型，发现具有平行 G-四链体结构的单链 DNA（ssDNA）可以与 G-四链体结合蛋白协同作用，在 GMVs 内部形成点状凝聚物。这种聚集行为依赖于 G-四链体的结构多样性，而可逆的聚集行为暗示了一种新的途径，可用于动态调节生物分子凝聚体的形成。这一发现代表了 G-四链体结合蛋白与 G-四链体介导的生物分子相分离之间的潜在联系，这将深入了解与活细胞内核酸调节的相分离相关的广泛的生物学过程。
