PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition
PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition
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DOI：
10.1242/dev.059287
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发表时间：
2011-05-01
期刊：
影响因子：
4.6
通讯作者：
Lin, Haifan
中科院分区：
文献类型：
--
作者：
Liu, Li;Qi, Hongying;Lin, Haifan
Nuage是一种生殖系特有的核周结构，在功能上仍然难以捉摸。最近，果蝇的Nuage被证明含有三个PIWI蛋白中的两个-Aubergine和ArgAerte 3(AG03)-这是生殖系发育所必需的。PIWI蛋白与PIWI相互作用的RNA(PiRNAs)结合，在表观遗传调控和转座子调控中发挥作用。在这里，我们报告了一个新的Nuage组分，PAPI(PIWIs的合作伙伴)，它包含一个Tudor结构域，并通过N-末端结构域上对称的二甲基化精氨酸残基与所有三个PIWI蛋白相互作用。在成体卵巢中，PAPI主要分布在胞浆内，并与AgO_3部分共存。PAPI对核抗原的定位不需要精氨酸甲基转移酶dPRMT5或AgO_3。然而，AG03在很大程度上是从Nuage中分离出来的，并且在没有PAPI或dPRMT5的情况下变得不稳定，这表明PAPI将PIWI蛋白招募到Nuage中来组装piRNA途径组件。正如预期的那样，PAPI缺乏导致转座子激活，表型复制piRNA突变体。这进一步表明，PAPI参与了转座子沉默的piRNA途径。此外，AgO_3和PAPI与P小体成分tral/ME31B复合体结合在一起，在tral突变卵巢中观察到转座子的激活。这表明在转座子沉默中，piRNA途径组分和mRNA降解的P-体组分之间存在物理和功能上的相互作用。总体而言，我们的研究揭示了Nuage在保护生殖系基因组免受通过piRNA途径有害的逆转录转座中的功能。
The nuage is a germline-specific perinuclear structure that remains functionally elusive. Recently, the nuage in Drosophila was shown to contain two of the three PIWI proteins - Aubergine and Argonaute 3 (AGO3) - that are essential for germline development. The PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and function in epigenetic regulation and transposon control. Here, we report a novel nuage component, PAPI (Partner of PIWIs), that contains a TUDOR domain and interacts with all three PIWI proteins via symmetrically dimethylated arginine residues in their N-terminal domain. In adult ovaries, PAPI is mainly cytoplasmic and enriched in the nuage, where it partially colocalizes with AGO3. The localization of PAPI to the nuage does not require the arginine methyltransferase dPRMT5 or AGO3. However, AGO3 is largely delocalized from the nuage and becomes destabilized in the absence of PAPI or dPRMT5, indicating that PAPI recruits PIWI proteins to the nuage to assemble piRNA pathway components. As expected, papi deficiency leads to transposon activation, phenocopying piRNA mutants. This further suggests that PAPI is involved in the piRNA pathway for transposon silencing. Moreover, AGO3 and PAPI associate with the P body component TRAL/ME31B complex in the nuage and transposon activation is observed in tral mutant ovaries. This suggests a physical and functional interaction in the nuage between the piRNA pathway components and the mRNA-degrading P-body components in transposon silencing. Overall, our study reveals a function of the nuage in safeguarding the germline genome against deleterious retrotransposition via the piRNA pathway.