Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs.
Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs.
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果蝇 YBX1 同源物 YPS 通过优先识别 5-甲基胞嘧啶 RNA 促进卵巢生殖系干细胞发育。
DOI：
10.1073/pnas.1910862117
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Ting Xie
中科院分区：
文献类型：
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作者：
Fan Zou;Renjun Tu;Bo Duan;Zhenlin Yang;Zhaohua Ping;Xiaoqing Song;Shiyuan Chen;Andrew Price;Hua Li;Allison Scott;Anoja Perera;Sisi Li;Ting Xie
5-甲基胞嘧啶 (m5C) 是一种存在于 tRNA 和 rRNA 中的 RNA 修饰，最近在 mRNA 中发现。尽管有人认为 m5C RNA 修饰可以调节多种生物学功能，但其是否影响成体干细胞的发育仍不清楚。在这项研究中，我们发现 Ypsilon schachtel (YPS) 是人 Y 盒结合蛋白 1 (YBX1) 的同源物，通过优先与含有 m5C 的 RNA 结合，促进果蝇卵巢中生殖系干细胞 (GSC) 的维持、增殖和分化。基因证明 YPS 在果蝇卵巢中具有 GSC 维持、增殖和子代分化的内在功能，而人 YBX1 可以在功能上替代 YPS 以支持正常的 GSC 发育。 YPS 和 YBX1 高度保守的冷休克结构域 (CSD) 在体外优先与 m5C RNA 结合。此外，YPS 还优先结合生殖细胞中含有 m5C 的 RNA，包括 mRNA。 YBX1 CSD-RNA 复合物的晶体结构表明疏水堆积和氢键对于 m5C 结合至关重要。 RNA 结合缺陷的 YPS 和 YBX1 蛋白的过度表达会破坏 GSC 的发育。综上所述，我们的研究结果表明 m5C RNA 修饰在成体干细胞发育中发挥着重要作用。
5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in theDrosophilaovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in theDrosophilaovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding–defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.