c-Fos Repression by Piwi Regulates Drosophila Ovarian Germline Formation and Tissue Morphogenesis.

c-Fos Repression by Piwi Regulates Drosophila Ovarian Germline Formation and Tissue Morphogenesis.
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DOI:
10.1371/journal.pgen.1006281
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发表时间:
2016-09
期刊:
影响因子:
4.5
通讯作者:
Peng JC
Peng JC
中科院分区:
生物学2区
文献类型:
--
作者:
Klein JD;Qu C;Yang X;Fan Y;Tang C;Peng JC

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黑腹果蝇Piwi在生殖系干细胞(GSCs)和体细胞生态位中发挥作用,调节GSC的自我更新和分化。Piwi如何影响GSCs在很大程度上是未知的。我们发现了Piwi和c-Fos在体细胞生态位中影响GSCs的遗传相互作用。c-Fos是一种影响许多细胞和发育过程的原癌基因。在野生型卵巢细胞中,c-Fos被Piwi转录后抑制,通过促进其3 '非翻译区(UTR)加工成Piwi相互作用的rna (pirna)来破坏c-Fos mRNA的稳定性。c-Fos 3 ' UTR足以触发piwi依赖性的GFP报告蛋白失稳。Piwi抑制体细胞生态位中的c-Fos以调节GSC的维持和分化,并抑制体细胞卵泡细胞中的c-Fos以影响体细胞组织紊乱、组织畸形发生、卵母细胞成熟阻滞和不育。黑腹果蝇卵巢由从GSCs分化而来的生殖细胞和为器官提供结构支持的卵巢体细胞组成。Piwi是果蝇卵巢GSC维持和分化所需的核糖核蛋白。Piwi通过影响gsc自主机制或体细胞生态位信号传导来实现这一功能。体细胞生态位由邻近GSC的细胞组成,这些细胞发出信号以促进GSC的功能。已知Piwi和pirna也抑制转座子。我们发现Piwi与体细胞生态位中的c-Fos基因相互作用,抑制卵巢体细胞中c-Fos的表达。Piwi通过介导其3 ' UTR产生pirna来破坏c-Fos mRNA的稳定性。Piwi抑制体细胞生态位中的c-Fos以促进GSC功能,并抑制卵巢体细胞中的c-Fos以影响细胞组织、组织形态发生和卵子产生。
Drosophila melanogaster Piwi functions within the germline stem cells (GSCs) and the somatic niche to regulate GSC self-renewal and differentiation. How Piwi influences GSCs is largely unknown. We uncovered a genetic interaction between Piwi and c-Fos in the somatic niche that influences GSCs. c-Fos is a proto-oncogene that influences many cell and developmental processes. In wild-type ovarian cells, c-Fos is post-transcriptionally repressed by Piwi, which destabilized the c-Fos mRNA by promoting the processing of its 3′ untranslated region (UTR) into Piwi-interacting RNAs (piRNAs). The c-Fos 3′ UTR was sufficient to trigger Piwi-dependent destabilization of a GFP reporter. Piwi represses c-Fos in the somatic niche to regulate GSC maintenance and differentiation and in the somatic follicle cells to affect somatic cell disorganization, tissue dysmorphogenesis, oocyte maturation arrest, and infertility. The Drosophila melanogaster ovary is consisted of germ cells differentiated from GSCs and ovarian somatic cells that provide structural support to the organ. Piwi is a ribonucleoprotein required for GSC maintenance and differentiation in the Drosophila ovary. Piwi does so by influencing GSC-autonomous mechanisms or the somatic niche signaling. The somatic niche is composed of cells adjacent to the GSC that signal to promote GSC functions. Piwi and piRNAs are also known to repress transposons. We found that Piwi genetically interacts with c-Fos in the somatic niche and represses c-Fos expression in the ovarian somatic cells. Piwi destabilizes the c-Fos mRNA by mediating the generation of piRNAs from its 3′ UTR. Piwi represses c-Fos in the somatic niche to promote GSC functions and in the somatic ovarian cells to influence cell organization, tissue morphogenesis, and egg production.
DOI: 10.1242/dev.01820
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