mRNA Regulation and Development, Institute of Human Genetics, UMR9002 CNRS-Univ Montpellier, 141 rue de la Cardonille, 34396, Montpellier Cedex 5, France.
Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Montpellier, France.
Cell Res. 2020 May;30(5):421-435. doi: 10.1038/s41422-020-0294-9. Epub 2020 Mar 4.
Piwi-interacting RNAs (piRNAs) and PIWI proteins are essential in germ cells to repress transposons and regulate mRNAs. In Drosophila, piRNAs bound to the PIWI protein Aubergine (Aub) are transferred maternally to the embryo and regulate maternal mRNA stability through two opposite roles. They target mRNAs by incomplete base pairing, leading to their destabilization in the soma and stabilization in the germ plasm. Here, we report a function of Aub in translation. Aub is required for translational activation of nanos mRNA, a key determinant of the germ plasm. Aub physically interacts with the poly(A)-binding protein (PABP) and the translation initiation factor eIF3. Polysome gradient profiling reveals the role of Aub at the initiation step of translation. In the germ plasm, PABP and eIF3d assemble in foci that surround Aub-containing germ granules, and Aub acts with eIF3d to promote nanos translation. These results identify translational activation as a new mode of mRNA regulation by Aub, highlighting the versatility of PIWI proteins in mRNA regulation.
Piwi 相互作用 RNA(piRNAs)和 PIWI 蛋白在生殖细胞中对于抑制转座子和调节 mRNA 至关重要。在果蝇中,与 PIWI 蛋白 Aubergine(Aub)结合的 piRNAs 通过母体传递到胚胎,并通过两种相反的作用来调节母体 mRNA 的稳定性。它们通过不完全碱基配对靶向 mRNA,导致其在体细胞中不稳定,而在生殖质中稳定。在这里,我们报告了 Aub 在翻译中的作用。Aub 对于 nanos mRNA 的翻译激活是生殖质的关键决定因素。Aub 与 poly(A)-结合蛋白 (PABP) 和翻译起始因子 eIF3 物理相互作用。多核糖体梯度分析揭示了 Aub 在翻译起始步骤中的作用。在生殖质中,PABP 和 eIF3d 在围绕含有 Aub 的生殖质颗粒的焦点中组装,Aub 与 eIF3d 一起促进 nanos 的翻译。这些结果确定了翻译激活是 Aub 调节 mRNA 的一种新方式,突显了 PIWI 蛋白在 mRNA 调节中的多功能性。