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Nat Cell Biol May 1, 2009; 11 (5): 652-8.

Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability.

Kirino Y , Kim N , de Planell-Saguer M , Khandros E , Chiorean S , Klein PS , Rigoutsos I , Jongens TA , Mourelatos Z .

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.

PubMed ID: 19377467
PMC ID: PMC2746449
Article link: Nat Cell Biol
Grant support: GM0720777 NIGMS NIH HHS , GM76621 NIGMS NIH HHS , NS046573 NINDS NIH HHS , NS056070 NINDS NIH HHS , R01 NS046573-04 NINDS NIH HHS , UL1RR024134 NCRR NIH HHS , R01 GM076621-01A1 NIGMS NIH HHS , R01 GM076621-02 NIGMS NIH HHS , R01 GM076621-03 NIGMS NIH HHS , R01 GM076621 NIGMS NIH HHS , R01 NS046573 NINDS NIH HHS , R01 NS056070 NINDS NIH HHS , UL1 RR024134 NCRR NIH HHS

Genes referenced: ago3 pgc pir piwil1 piwil2 prmt5 slc22a18

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