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

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.

SUBMITTER: Wang X

PROVIDER: S-EPMC11197489 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Wang Xiuzhi X Wang Mengke M Dai Xinyuan X Han Xiao X Zhou Yu Y Lai Weiyi W Zhang Liyuan L Yang Ying Y Chen Yusheng Y Wang Hailin H Zhao Yong-Liang YL Shen Bin B Zhang Yuhan Y Huang Ying Y Yang Yun-Gui YG

Fundamental research 20211208 1

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 ...[more]

PMID: 38933916

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