Anne, J., Ollo, R., Ephrussi, A. & Mechler, B.M. Arginine methyltransferase Capsuleen is essential for methylation of spliceosomal Sm proteins and germ cell formation in Drosophila. Development 134, 137-146

Department of Developmental Genetics, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Development (Impact Factor: 6.46). 02/2007; 134(1):137-46. DOI: 10.1242/dev.02687
Source: PubMed


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.

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Available from: Bernard M Mechler, Oct 09, 2015
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    • "This protein arginine methyltransferase has also been suggested to be a key player of PGC specification or development. This is based on knockout (KO) experiments of the Drosophila Prmt5 homologue (dart5), which leads to infertility (Anne et al, 2007). In the mouse, PRMT5 has been hypothesised to induce germline fate as an interactor of BLIMP1 (Ancelin et al, 2006). "
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    ABSTRACT: Primordial germ cells (PGCs) are the embryonic precursors of the germ cell lineage that form sperm and egg cells. It is of great importance to preserve the germline from DNA damage and potentially from epimutations in order to ensure the survival of future generations. Recent research highlights the role of the protein arginine methyltransferase 5 (PRMT5) as an important player in DNA protection during germline development in the mouse (Kim et al, & Li et al,). Protecting the genetic integrity of the germline is of outmost importance. Two novel studies establish multiple roles of PRMT5 in safe-guarding genomic integrity of PGCs, beyond earlier proposed roles in the induction of germline fate. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
    The EMBO Journal 02/2015; 34(6). DOI:10.15252/embj.201591054 · 10.43 Impact Factor
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    • "In Drosophila melanogaster, SmB and SmD3 are enriched at the posterior pole of developing oocytes [21,22], and a hypomorphic mutation in SmD3 causes mislocalization of oskar mRNPs and pronounced defects in germ cell specification that are independent from splicing [21]. Moreover, loss of the Sm protein methyltransferase PRMT5 results in failure to specify the germline [21,23,24]. Furthermore, a genetic screen for modifiers of FMR1 (Fragile X mental retardation 1) in Drosophila identified SmD3 as a suppressor of dFMR1’s translational repression function, and SmD3 and dFMR1 were found to colocalize within neuronal mRNP granules [25]. "
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    ABSTRACT: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism.
    Genome biology 01/2014; 15(1):R7. DOI:10.1186/gb-2014-15-1-r7 · 10.81 Impact Factor
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    • "Genes such as vasa, nanos, and piwi also function in mouse PGC fate, but they are expressed and appear to function much later in development. Interestingly , capsuleen/dart5, a homologue of Drosophila prmt5, has been shown to regulate germ-cell specification and spermatocyte specification in females and males, respectively (Gonsalvez et al., 2006; Anne et al., 2007). Dart5 mutants show disrupted localization of tudor, an essential gene for polar granule assembly and pole cell specialization in Drosophila (Thomson and Lasko, 2004). "
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    ABSTRACT: Formation of the germline in an embryo marks a fresh round of reproductive potential, yet the developmental stage and location within the embryo where the primordial germ cells (PGCs) form differs wildly among species. In most animals, the germline is formed either by an inherited mechanism, in which maternal provisions within the oocyte drive localized germ-cell fate once acquired in the embryo, or an inductive mechanism that involves signaling between cells that directs germ-cell fate. The inherited mechanism has been widely studied in model organisms such as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis, and Danio rerio. Given the rapid generation time and the effective adaptation for laboratory research of these organisms, it is not coincidental that research on these organisms has led the field in elucidating mechanisms for germline specification. The inductive mechanism, however, is less well understood and is studied primarily in the mouse (Mus musculus). In this review, we compare and contrast these two fundamental mechanisms for germline determination, beginning with the key molecular determinants that play a role in the formation of germ cells across all animal taxa. We next explore the current understanding of the inductive mechanism of germ-cell determination in mice, and evaluate the hypotheses for selective pressures on these contrasting mechanisms. We then discuss the hypothesis that the transition between these determination mechanisms, which has happened many times in phylogeny, is more of a continuum than a binary change. Finally, we propose an analogy between germline determination and sex determination in vertebrates-two of the milestones of reproduction and development-in which animals use contrasting strategies to activate similar pathways. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 08/2013; 80(8). DOI:10.1002/mrd.22151 · 2.53 Impact Factor
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