Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG); Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oehonmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
J Biochem. 2021 Jul 3;169(5):527-533. doi: 10.1093/jb/mvab018.
Cellular liquid-liquid phase separation is a physiologically inevitable phenomenon in molecularly crowded environments inside cells and serves to compartmentalize biomolecules to facilitate several functions, forming cytoplasmic and nuclear RNA granules. Abnormalities in the phase separation process in RNA granules are implicated in the onset of several neurodegenerative diseases; the initial liquid-like phase-separated droplets containing pathogenic proteins are prone to aberrantly mature into solid-like droplets. RNAs are involved in the maturation of physiological and pathological RNA granules and are essential for governing the fate of phase-transition processes. Notably, RNA G-quadruplex (G4RNA), which is the secondary structure of nucleic acids that are formed in guanine-rich sequences, appears to be an advantageous scaffold for RNA-derived phase separation because of its multivalent interactions with RNAs and RNA-binding proteins. Here, we summarize the properties of RNA granules in physiological and pathological phase separation and discuss the potential roles of G4RNA in granules.
细胞液-液相分离是细胞内分子拥挤环境中一种生理上不可避免的现象，它将生物分子分隔成区室以促进多种功能，形成细胞质和核 RNA 颗粒。RNA 颗粒中相分离过程的异常与几种神经退行性疾病的发生有关；最初含有致病蛋白的类似液体的相分离液滴容易异常成熟为类似固体的液滴。RNA 参与生理和病理 RNA 颗粒的成熟，对于控制相变过程的命运至关重要。值得注意的是，RNA 四链体 (G4RNA) 是富含鸟嘌呤序列形成的核酸的二级结构，由于其与 RNA 和 RNA 结合蛋白的多价相互作用，似乎是 RNA 衍生相分离的有利支架。在这里，我们总结了生理和病理相分离中 RNA 颗粒的特性，并讨论了 G4RNA 在颗粒中的潜在作用。
