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PIWI

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Argonaute/Piwi家族的蛋白结构

PiwiArgonaute蛋白质家族的一个结构域,同时也是部分Argonaute家族蛋白(特指与piRNA结合者)的通称,最早在黑腹果蝇中发现,为“P元件英语P element诱导的小睾丸”(P-element Induced WImpy testis)之简称[1]。Argonaute/Piwi家族的蛋白N端有一PAZ结构域德语PAZ-Domäne可与小RNA3′端的单股突出碱基结合,中间有MID结构域与小RNA5′端的磷酸基结合,C端则为具内切酶活性的Piwi结构域[2][3]

一般而言Argonaute家族的蛋白与miRNAsiRNA(长约20nt)结合,Piwi家族的蛋白则与piRNA(长约30nt)结合[2],主要在睾丸精原细胞中表现,Piwi蛋白与piRNA结合后可进入细胞核中造成目标DNA的DNA甲基化组蛋白甲基化表观遗传修饰以抑制基因表现,也可在细胞质中抑制目标mRNA转译[4]。Piwi-piRNA的主要功能可能为抑制精原细胞基因组中自私的基因元件(如反转录转座子)表现,Piwi蛋白的缺陷可能导致精子发生异常[5][6],但许多哺乳类的体细胞亦有表现Piwi蛋白与piRNA。

人类基因组中已知有4个Piwi蛋白(PIWI样蛋白1-4,又称HIWI蛋白1-4)[7][8],小鼠的Piwi蛋白则称为MIWI蛋白[9]

参考文献

  1. ^ Lin H, Spradling AC. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development. 1997, 124 (12): 2463–2476. PMID 9199372. doi:10.1242/dev.124.12.2463. 
  2. ^ 2.0 2.1 Zeng, Lei; Zhang, Qiang; Yan, Kelley; Zhou, Ming-Ming. Structural insights into piRNA recognition by the human PIWI-like 1 PAZ domain. Proteins: Structure, Function, and Bioinformatics. 2011-06-01, 79 (6): 2004–2009. ISSN 1097-0134. PMC 3092821可免费查阅. PMID 21465557. doi:10.1002/prot.23003. 
  3. ^ Wei, Kai-Fa; Wu, Ling-Juan; Chen, Juan; Chen, Yan-feng; Xie, Dao-Xin. Structural evolution and functional diversification analyses of argonaute protein. Journal of Cellular Biochemistry. 2012, 113 (8): 2576–2585. ISSN 1097-4644. PMID 22415963. S2CID 25990631. doi:10.1002/jcb.24133. 
  4. ^ Lindse K. Piwi-RNAs, the Defenders of the Genome. 2013 [2022-08-14]. (原始内容存档于2022-03-07). 
  5. ^ Mani S, Juliano C. Untangling the Web: The Diverse Functions of the PIWI/piRNA Pathway. Mol. Reprod. Dev. 2013, 80 (8): 632–664. PMC 4234069可免费查阅. PMID 23712694. doi:10.1002/mrd.22195. 
  6. ^ Ozata DM, Gainetdinov I, Zoch A, Phillip D, Zamore PD. PIWI-interacting RNAs: small RNAs with big functions (PDF). Nature Reviews Genetics. 2019, 20 (2): 89–108 [2022-08-14]. PMID 30446728. S2CID 53565676. doi:10.1038/s41576-018-0073-3. (原始内容存档 (PDF)于2022-08-18). 
  7. ^ Tian Y, Simanshu D, Ma J, Patel D. Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains. Proc. Natl. Acad. Sci. USA. 2010, 108 (3): 903–910. PMC 3024652可免费查阅. PMID 21193640. doi:10.1073/pnas.1017762108可免费查阅. 
  8. ^ Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002, 21 (25): 3988–99. PMID 12037681. doi:10.1038/sj.onc.1205505可免费查阅. 
  9. ^ Deng W, Lin H. miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell. 2002, 2 (6): 819–30. PMID 12062093. doi:10.1016/s1534-5807(02)00165-x可免费查阅.