RNA 5-methylcytosine regulates YBX2-dependent liquid-liquid phase separation.

RNA 5 - 甲基胞嘧啶调节 YBX2 依赖性液 - 液相分离。

• 发表时间: 2022 Jan
• 来源期刊: Fundam Res
• DOI: 10.1016/j.fmre.2021.10.008
• PMID: 38933916
• 文章类型: Journal Article
• 作者列表: Wang X,Wang M,Dai X,Han X,Zhou Y,Lai W,Zhang L,Yang Y,Chen Y,Wang H,Zhao YL,Shen B,Zhang Y,Huang Y,Yang YG

关键词: Liquid droplet; Phase separation; RNA m5C; RNA modification; YBX2

Abstract

5-Methylcytosine (m5C) is one of the most prevalent internal modifications of messenger RNA (mRNA) in higher eukaryotes. Here we report that Y box protein 2 (YBX2) serves as a novel mammalian m5C binding protein to undergo liquid-liquid phase separation (LLPS) both in vivo and in vitro, and this YBX2-dependent LLPS is enhanced by m5C marked RNA. Furthermore, the crystal structure assay revealed that W100, as a distinct m5C binding site of YBX2, is critical in mediating YBX2 phase separation. Our study resolved the relationship between RNA m5C and phase separation, providing a clue for a new regulatory layer of epigenetics.

摘要

5-甲基胞嘧啶（m5C）是高等真核生物中信使RNA（mRNA）最普遍的内部修饰之一。在这里，我们报道Y盒蛋白2（YBX2）作为一种新型的哺乳动物m5C结合蛋白，在体内和体外进行液-液相分离（LLPS），这种依赖YBX2的LLPS被m5C标记的RNA增强。此外，晶体结构分析表明，W100作为YBX2的独特m5C结合位点，在介导YBX2相分离中至关重要。我们的研究解决了RNAm5C和相分离之间的关系，为表观遗传学的新调控层提供了线索。