mRNA Regulation and Development, Institute of Human Genetics, CNRS UPR1142, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France.
Stem Cell Reports. 2013 Nov 7;1(5):411-24. doi: 10.1016/j.stemcr.2013.09.007. eCollection 2013.
Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation.
转译调控在果蝇卵巢生殖干细胞（GSC）生物学中起着至关重要的作用。GSC 的自我更新需要两种转译抑制剂，Nanos（Nos）和Pumilio（Pum），它们抑制干细胞中分化因子的表达。这种转译抑制的分子机制尚不清楚。在这里，我们表明 CCR4 脱腺苷酶对于 GSC 的自我更新是必需的，并且 Nos 和 Pum 通过将其募集到特定的 mRNA 上来发挥作用。我们确定 mei-P26 mRNA 是 Nos/Pum/CCR4 在 GSCs 中转译抑制的直接和主要靶标。mei-P26 编码一种 Trim-NHL 肿瘤抑制因子家族的蛋白质，在干细胞谱系中具有保守功能。我们表明，CCR4 对 Mei-P26 表达的精细调节在 GSC 的自我更新中起着关键作用。这些结果确定了 Nos/Pum 在 GSC 自我更新中的功能的分子机制，并揭示了 CCR4-NOT 介导的脱腺苷化在调节 GSC 自我更新和分化之间的平衡中的作用。
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