5-Methylcytosine(m^(5)C)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 m^(5)C binding protein to und...5-Methylcytosine(m^(5)C)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 m^(5)C binding protein to undergo liquid-liquid phase separation(LLPS)both in vivo and in vitro,and this YBX2-dependent LLPS is enhanced by m^(5)C marked RNA.Furthermore,the crystal structure assay revealed that W100,as a distinct m^(5)C binding site of YBX2,is critical in mediating YBX2 phase separation.Our study resolved the relationship between RNA m^(5)C and phase separation,providing a clue for a new regulatory layer of epigenetics.展开更多
基金the National Natural Science Foundation of China(Grants No.32030058,91940302,91940304,91940000 and 92053115)the fellowship of China Postdoctoral Science Foundation(Grant No.2020M670986)+3 种基金the National Key R&D Program of China(Grants No.2018YFA0109700,2019YFA0801702 and 2019YFA0802201)Beijing Nova Program(Grant No.Z201100006820104)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.CAS2018133)the Open Research Fund of the National Center for Protein Sciences at Peking University in Beijing.We thank the National Center for Protein Science Shanghai for their instrumental support and technical assistance.We thank the staff from the BL18U1 beamline at Shanghai Synchrotron Radiation Facility for assistance during data collection.
文摘5-Methylcytosine(m^(5)C)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 m^(5)C binding protein to undergo liquid-liquid phase separation(LLPS)both in vivo and in vitro,and this YBX2-dependent LLPS is enhanced by m^(5)C marked RNA.Furthermore,the crystal structure assay revealed that W100,as a distinct m^(5)C binding site of YBX2,is critical in mediating YBX2 phase separation.Our study resolved the relationship between RNA m^(5)C and phase separation,providing a clue for a new regulatory layer of epigenetics.
