The Sm-protein methyltransferase, dart5, is essential for germ-cell specification and maintenance
The Sm-protein methyltransferase, dart5, is essential for germ-cell specification and maintenance
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DOI：
10.1016/j.cub.2006.04.037
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发表时间：
2006-06-06
期刊：
影响因子：
9.2
通讯作者：
Matera, A. Gregory
中科院分区：
文献类型：
--
作者：
Gonsalvez, Graydon B.;Rajendra, T. K.;Matera, A. Gregory
背景：剪接体Sm蛋白的C-末端尾部含有对称的二甲基精氨酸（sDMA）残基。这种翻译后修饰在小核核糖核蛋白（snRNP）和前体mRNA剪接的生物发生中的精确功能在很大程度上仍然是未知的。在这里，我们研究的有机体和细胞的后果损失的对称二甲基化的Sm蛋白在Drosophila.Results：飞镖，飞直系同源的人PRMT 5的遗传中断，结果在sDMA残基spliceosomal Sm蛋白的完全丧失。类似地，valois，一个以前的特点grandchildless基因，也需要sDMA修饰的Sm蛋白。在没有darts的情况下，snRNP生物合成令人惊讶地不受影响，纯合突变动物是完全可行的。相反，Darts蛋白是雄性精母细胞成熟和雌性生殖细胞特化所必需的。由darts突变体产下的胚胎不能形成极细胞，并且Tudor定位在第10阶段卵母细胞中被破坏。Darts的转基因表达只在雌性生殖系内拯救极细胞形成，而无处不在的表达拯救了Sm蛋白和雄性sterility.Conclusions的SDMA修饰：我们已经表明，Darts介导的Sm蛋白的甲基化对于snRNP的生物发生是不必要的。这些结果揭示了飞镖在生殖细胞和精母细胞成熟中的特殊作用。由于darts和valois的破坏导致了sDMA修饰的Sm蛋白的特异性丢失，elegans的研究表明Sm蛋白是生殖颗粒定位所必需的，我们认为Sm蛋白甲基化是生殖细胞发育中的一个关键事件。
Background: The C-terminal tails of spliceosomal Sm proteins contain symmetrical dimethylarginine (sDMA) residues in vivo. The precise function of this posttranslational modification in the biogenesis of small nuclear ribonucleoproteins (snRNPs) and pre-mRNA splicing remains largely uncharacterized. Here, we examine the organismal and cellular consequences of loss of symmetric dimethylation of Sm proteins in Drosophila.Results: Genetic disruption of darts, the fly ortholog of human PRMT5, results in the complete loss of sDMA residues on spliceosomal Sm proteins. Similarly, valois, a previously characterized grandchildless gene, is also required for sDMA modification of Sm proteins. In the absence of darts, snRNP biogenesis is surprisingly unaffected, and homozygous mutant animals are completely viable. Instead, Darts protein is required for maturation of spermatocytes in males and for germ-cell specification in females. Embryos laid by darts mutants fail to form pole cells, and Tudor localization is disrupted in stage 10 oocytes. Transgenic expression of Darts exclusively within the female germline rescues pole-cell formation, whereas ubiquitous expression rescues sDMA modification of Sm proteins and male sterility.Conclusions: We have shown that Darts-mediated methylation of Sm proteins is not essential for snRNP biogenesis. The results uncover a novel role for darts in specification of the germline and in spermatocyte maturation. Because disruption of both darts and valois causes the specific loss of sDMA-modified Sm proteins and studies in C. elegans show that Sm proteins are required for germ-granule localization, we propose that Sm protein methylation is a pivotal event in germ-cell development.