Fundamental Research (Jan 2022)

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,
  • Yusheng Chen,
  • Hailin Wang,
  • Yong-Liang Zhao,
  • Bin Shen,
  • Yuhan Zhang,
  • Ying Huang,
  • Yun-Gui Yang

Journal volume & issue
Vol. 2, no. 1
pp. 48 – 55

Abstract

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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.

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