Kirino Yohei, Kim Namwoo, de Planell-Saguer Mariàngels, Khandros Eugene, Chiorean Stephanie, Klein Peter S, Rigoutsos Isidore, Jongens Thomas A, Mourelatos Zissimos
Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nat Cell Biol. 2009 May;11(5):652-8. doi: 10.1038/ncb1872. Epub 2009 Apr 19.
Piwi family proteins are essential for germline development and bind piwi-interacting RNAs (piRNAs). The grandchildless gene aub of Drosophila melanogaster encodes the piRNA-binding protein Aubergine (Aub), which is essential for formation of primordial germ cells (PGCs). Here we report that Piwi family proteins of mouse, Xenopus laevis and Drosophila contain symmetrical dimethylarginines (sDMAs). We found that Piwi proteins are expressed in Xenopus oocytes and we identified numerous Xenopus piRNAs. We report that the Drosophila homologue of protein methyltransferase 5 (dPRMT5, csul/dart5), which is also the product of a grandchildless gene, is required for arginine methylation of Drosophila Piwi, Ago3 and Aub proteins in vivo. Loss of dPRMT5 activity led to a reduction in the levels of piRNAs, Ago3 and Aub proteins, and accumulation of retrotransposons in the Drosophila ovary. Our studies explain the relationship between aub and dPRMT5 (csul/dart5) genes by demonstrating that dPRMT5 is the enzyme that methylates Aub. Our findings underscore the significance of sDMA modification of Piwi proteins in the germline and suggest an interacting pathway of genes that are required for piRNA function and PGC specification.
Piwi家族蛋白对于生殖系发育至关重要,并与Piwi相互作用RNA(piRNA)结合。果蝇的“无孙辈”基因aub编码piRNA结合蛋白茄子(Aub),这对原始生殖细胞(PGC)的形成至关重要。在此我们报告,小鼠、非洲爪蟾和果蝇的Piwi家族蛋白含有对称二甲基精氨酸(sDMA)。我们发现Piwi蛋白在非洲爪蟾卵母细胞中表达,并且我们鉴定出了众多非洲爪蟾piRNA。我们报告,蛋白甲基转移酶5(dPRMT5,csul/dart5)的果蝇同源物,其也是一个“无孙辈”基因的产物,在体内对于果蝇Piwi、Ago3和Aub蛋白的精氨酸甲基化是必需的。dPRMT5活性丧失导致果蝇卵巢中piRNA、Ago3和Aub蛋白水平降低,以及反转录转座子积累。我们的研究通过证明dPRMT5是甲基化Aub的酶,解释了aub和dPRMT5(csul/dart5)基因之间的关系。我们的发现强调了Piwi蛋白的sDMA修饰在生殖系中的重要性,并提示了piRNA功能和PGC特化所需基因的相互作用途径。