PIWI
Piwi是Argonaute蛋白質家族的一個結構域，同時也是部分Argonaute家族蛋白（特指與piRNA結合者）的通稱，最早在黑腹果蠅中發現，為「P元件誘導的小睪丸」（P-element Induced WImpy testis）之簡稱[1]。Argonaute/Piwi家族的蛋白N端有一PAZ結構域可與小RNA3′端的單股突出鹼基結合，中間有MID結構域與小RNA5′端的磷酸基結合，C端則為具內切酶活性的Piwi結構域[2][3]。
一般而言Argonaute家族的蛋白與miRNA或siRNA（長約20nt）結合，Piwi家族的蛋白則與piRNA（長約30nt）結合[2]，主要在睪丸的精原細胞中表現，Piwi蛋白與piRNA結合後可進入細胞核中造成目標DNA的DNA甲基化和組蛋白甲基化等表觀遺傳修飾以抑制基因表現，也可在細胞質中抑制目標mRNA的轉譯[4]。Piwi-piRNA的主要功能可能為抑制精原細胞基因組中自私的基因元件（如反轉錄轉座子）表現，Piwi蛋白的缺陷可能導致精子發生異常[5][6]，但許多哺乳類的體細胞亦有表現Piwi蛋白與piRNA。
人類基因組中已知有4個Piwi蛋白（PIWI樣蛋白1－4，又稱HIWI蛋白1－4）[7][8]，小鼠的Piwi蛋白則稱為MIWI蛋白[9]。
參考文獻 编辑
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- ^ 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
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- ^ 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.
- ^ Lindse K. Piwi-RNAs, the Defenders of the Genome. 2013 [2022-08-14]. （原始内容存档于2022-03-07）.
- ^ 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 . PMID 23712694. doi:10.1002/mrd.22195.
- ^ 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）.
- ^ 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 . PMID 21193640. doi:10.1073/pnas.1017762108 .
- ^ 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 .
- ^ 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 .
