RNA 5-methylcytosine regulates YBX2-dependent liquid-liquid phase separation
Xiuzhi Wang, Mengke Wang, Xinyuan Dai, Xiao Han, Yu Zhou, Weiyi Lai, Liyuan Zhang, Ying Yang, Ying Yang, Yusheng Chen, Hailin Wang, Yongliang Zhao, Bin Shen, Yuhan Zhang, Ying Huang, Yun‐Gui Yang, Yun‐Gui Yang
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.