Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation.
Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation.
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DOI：
10.1016/j.devcel.2016.02.010
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发表时间：
2016-03-07
影响因子：
11.8
通讯作者：
Buszczak M
中科院分区：
文献类型：
--
作者：
Carreira-Rosario A;Bhargava V;Hillebrand J;Kollipara RK;Ramaswami M;Buszczak M
RNA结合Fox（Rbfox）蛋白在调节选择性剪接中具有公认的作用，但特定的Rbfox同种型缺乏核定位信号并在细胞质中积累。这些蛋白质的潜在剪接独立功能仍然未知。在这里，我们证明，细胞质果蝇Rbfox1调节生殖细胞的发展，并抑制翻译的mRNA含有（U）GCAUG元件在其3 ′ UTR。在生殖细胞囊肿分化过程中，Rbfox1靶向pumilio mRNA的不稳定和翻译沉默，从而促进生殖细胞发育。pumilio的错误表达导致生殖系肿瘤的形成，其中包含破裂和去分化回单个有丝分裂活性细胞的包囊。这些结果共同揭示了细胞质Rbfox家族成员调节特定靶mRNA的翻译。在果蝇卵巢中，这种活性提供了一种遗传屏障，阻止生殖细胞恢复到早期的发育状态。Rbfox蛋白调节mRNA翻译的发现对Rbfox相关疾病具有意义。
RNA-binding Fox (Rbfox) proteins have well-established roles in regulating alternative splicing, but specific Rbfox isoforms lack nuclear localization signals and accumulate in the cytoplasm. The potential splicing-independent functions of these proteins remain unknown. Here we demonstrate that cytoplasmic Drosophila Rbfox1 regulates germ cell development and represses the translation of mRNAs containing (U)GCAUG elements within their 3′ UTRs. During germline cyst differentiation, Rbfox1 targets pumilio mRNA for destabilization and translational silencing, thereby promoting germ cell development. Mis-expression of pumilio results in the formation of germline tumors, which contain cysts that breakdown and dedifferentiate back to single, mitotically active cells. Together these results reveal that cytoplasmic Rbfox family members regulate the translation of specific target mRNAs. In the Drosophila ovary, this activity provides a genetic barrier that prevents germ cells from reverting back to an earlier developmental state. The finding that Rbfox proteins regulate mRNA translation has implications for Rbfox related diseases.