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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains
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Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains

机译：Piwi PAZ（Piwi / Argonaute / Zwille）域识别piRNA 2'-O-甲基化3'-端的结构基础

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摘要

Argonaute and Piwi proteins are key players in the RNA silencing pathway, with the former Interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter targets piwi-interacting RNAs (piRNAs) that are 2' -O-methylated (2-OCH_3) at their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role in genome defense against transposable elements, thereby protecting the genome against transposon-induced defects in gametogen-esis and fertility. Humans contain four Piwi family proteins designated Hiwi1, Hiwi2, Hiwi3, and Hili. We report on the structures of Hili-PAZ (Piwi/Argonaute/Zwille) domain in the free state and Hiwi1 PAZ domain bound to self-complementary 14-mer RNAs (12-bp + 2-nt overhang) containing 2'-OCH_3 and 2'-OH at their 3' ends. These structures explain the molecular basis underlying accommodation of the 2'-OCH_3 group within a preformed Hiwii PAZ domain binding pocket, whose hydrophobic characteristics account for the preferential binding of 2'-OCH_3 over 2' -OH 3' ends. These results contrast with the more restricted binding pocket for the human Ago1 PAZ domain, which exhibits a reverse order, with preferential binding of 2' -OH over 2'-OCH_3 3' ends.
机译：Argonaute和Piwi蛋白是RNA沉默途径中的关键角色，前者与micro-RNA（miRNA）和siRNA相互作用，而后者则与2'-O-甲基化（2-OCH_3）的piwi相互作用RNA（piRNA）相互作用。 ）的3'端。胚系特异的piRNA和Piwi蛋白在基因组防御转座因子中起着关键作用，从而保护基因组免受转座子诱导的配子发生性和生育力缺陷。人类含有四种名为Hiwi1，Hiwi2，Hiwi3和Hili的Piwi家族蛋白。我们报告在自由状态下的Hili-PAZ（Piwi / Argonaute / Zwille）域和与包含2'-OCH_3的自我互补14-mer RNAs（12-bp + 2-nt突出端）结合的Hiwi1 PAZ域的结构。 2'-OH在其3'末端。这些结构解释了在预先形成的Hiwii PAZ域结合口袋中容纳2'-OCH_3基团的分子基础，其疏水特性解释了2'-OCH_3相对于2'-OH 3'端优先结合。这些结果与人Ago1 PAZ结构域的结合口袋的限制性更强形成对比，后者表现出相反的顺序，与2'-OCH_3 3'端相比优先结合2'-OH。

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    Yuan Tian; Dhirendra K. Simanshu; Jin-Biao Ma; Dinshaw J. Patel;

  • 作者单位

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065,Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, NY 10065;

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065,Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294;

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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