Arginine methyltransferase Capsuléen is essential for methylation of spliceosomal Sm proteins and germ cell formation inDrosophila

Abstract

Although arginine modification has been implicated in a number of cellular processes, the in vivo requirement of protein arginine methyltransferases (PRMTs) in specific biological processes remain to be clarified. In this study we characterize the Drosophila PRMT Capsuléen, homologous to human PRMT5. During Drosophila oogenesis, catalytic activity of Capsuléen is necessary for both the assembly of the nuage surrounding nurse cell nuclei and the formation of the pole plasm at the posterior end of the oocyte. In particular, we show that the nuage and pole plasm localization of Tudor, an essential component for germ cell formation, are abolished in csul mutant germ cells. We identify the spliceosomal Sm proteins as in vivo substrates of Capsuléen and demonstrate that Capsuléen, together with its associated protein Valois, is essential for the synthesis of symmetric di-methylated arginyl residues in Sm proteins. Finally, we show that Tudor can be targeted to the nuage in the absence of Sm methylation by Capsuléen, indicating that Tudor localization and Sm methylation are separate processes. Our results thus reveal the role of a PRMT in protein localization in germ cells.

Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi

“…The RG/RA clusters at the N-termini of Miwi and Mili are potentially methylated by specific protein arginine methyltransferases (PRMTs), especially PRMT5, which has a Drosophila counterpart (dPRMT5) with crucial roles in germ cell specification and maintenance, and gives a similar mutant phenotype to Drosophila tudor (26,27). Kirino et al (28) have demonstrated that dPRMT5 is required for arginine methylation of Drosophila Piwi proteins and their stability, reinforcing the functional significance of arginine methylation in germ cell biology.…”

Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3′ UTR

“…RGG motifs are also targets for arginine methyltransferases, and arginine methylation has been linked to modulating the RNA-binding activity of heterogeneous nuclear RNP (hnRNP) A1 (Kim et al 1997). It is tempting to speculate that the RNA-binding activity of Vas might be similarly modulated, perhaps through the activity of the arginine methyltransferase Capsulé en, which like Vas is essential for germ cell specification (Gonsalvez et al 2006;Anne et al 2007).…”

Mitochondrial protein BmPAPI modulates the length of mature piRNAs

“…PIWI proteins from various species commonly contain the sDMA motif typically at their N terminus, and evolutionarily conserved presence of PIWI sDMAs has been confirmed in mice, Drosophila, zebrafish, and Xenopus Kirino et al 2009;Nishida et al 2009;Reuter et al 2009;Vagin et al 2009;Huang et al 2011b). The PIWI sDMAs are mediated by PRMT5 methyltransferase, and their functional importance has been demonstrated by the studies on Drosophila null mutants of PRMT5, in which sDMAs are absent in any of the three Drosophila PIWI proteins, leading to transposon activation and defects in germline development (Gonsalvez et al 2006;Anne et al 2007;Kirino et al 2009). The identification of PIWI sDMAs suggested a possible interactive network of PIWI proteins with proteins containing TUDOR domain that constitutes the TUDOR "royal family" of protein domains (Maurer-Stroh et al 2003).…”