Zfrp8/PDCD2 Interacts with RpS2 Connecting Ribosome Maturation and Gene-Specific Translation.
Zfrp8/PDCD2 Interacts with RpS2 Connecting Ribosome Maturation and Gene-Specific Translation.
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DOI：
10.1371/journal.pone.0147631
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Steward R
中科院分区：
文献类型：
--
作者：
Minakhina S;Naryshkina T;Changela N;Tan W;Steward R
Zfrp8/PDCD2是一种高度保守的蛋白质，对果蝇和哺乳动物的干细胞维持都是必不可少的。它也是癌细胞等快速增殖的细胞所必需的。我们以前的研究表明，Zfrp8在mRNP(信使核糖核蛋白)复合体的形成中起作用，也控制特定转座元件(TES)的RNA。在这里，我们发现在Zfrp8/PDCD2敲除(KD)卵巢中，特定的mRNAs和TE转录本显示核积累增加。我们还发现Zfrp8/PDCD2通过与RpS2(US5)直接相互作用而与(40S)小核糖体亚基相互作用。通过研究内源和转基因荧光标记的核糖体蛋白的分布，我们证明Zfrp8/PDCD2调节核糖体小亚基(40S)组成成分的细胞质水平，但不控制核糖体蛋白的核/核仁定位。我们的结果表明，Zfrp8/PDCD2在核糖体组装的后期发挥作用，可能调节特定的mRNA-RNPs与核糖体小亚基的结合，最终控制它们的细胞质定位和翻译。
Zfrp8/PDCD2 is a highly conserved protein essential for stem cell maintenance in both flies and mammals. It is also required in fast proliferating cells such as cancer cells. Our previous studies suggested that Zfrp8 functions in the formation of mRNP (mRNA ribonucleoprotein) complexes and also controls RNA of select Transposable Elements (TEs). Here we show that in Zfrp8/PDCD2 knock down (KD) ovaries, specific mRNAs and TE transcripts show increased nuclear accumulation. We also show that Zfrp8/PDCD2 interacts with the (40S) small ribosomal subunit through direct interaction with RpS2 (uS5). By studying the distribution of endogenous and transgenic fluorescently tagged ribosomal proteins we demonstrate that Zfrp8/PDCD2 regulates the cytoplasmic levels of components of the small (40S) ribosomal subunit, but does not control nuclear/nucleolar localization of ribosomal proteins. Our results suggest that Zfrp8/PDCD2 functions at late stages of ribosome assembly and may regulate the binding of specific mRNA-RNPs to the small ribosomal subunit ultimately controlling their cytoplasmic localization and translation.