Barckmann Bridlin, Pierson Stéphanie, Dufourt Jérémy, Papin Catherine, Armenise Claudia, Port Fillip, Grentzinger Thomas, Chambeyron Séverine, Baronian Grégory, Desvignes Jean-Pierre, Curk Tomaz, Simonelig Martine
mRNA Regulation and Development, Institut de Génétique Humaine, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
RNA Silencing and Control of Transposition, Institut de Génétique Humaine, CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
Cell Rep. 2015 Aug 18;12(7):1205-16. doi: 10.1016/j.celrep.2015.07.030. Epub 2015 Aug 6.
The Piwi-interacting RNA (piRNA) pathway plays an essential role in the repression of transposons in the germline. Other functions of piRNAs such as post-transcriptional regulation of mRNAs are now emerging. Here, we perform iCLIP with the PIWI protein Aubergine (Aub) and identify hundreds of maternal mRNAs interacting with Aub in the early Drosophila embryo. Gene expression profiling reveals that a proportion of these mRNAs undergo Aub-dependent destabilization during the maternal-to-zygotic transition. Strikingly, Aub-dependent unstable mRNAs encode germ cell determinants. iCLIP with an Aub mutant that is unable to bind piRNAs confirms piRNA-dependent binding of Aub to mRNAs. Base pairing between piRNAs and mRNAs can induce mRNA cleavage and decay that are essential for embryonic development. These results suggest general regulation of maternal mRNAs by Aub and piRNAs, which plays a key developmental role in the embryo through decay and localization of mRNAs encoding germ cell determinants.
Piwi相互作用RNA(piRNA)通路在生殖系中转座子的抑制中起着至关重要的作用。piRNA的其他功能,如mRNA的转录后调控,目前也正在显现出来。在这里,我们用PIWI蛋白茄子(Aub)进行了个体交叉连接免疫沉淀(iCLIP),并鉴定出数百种在早期果蝇胚胎中与Aub相互作用的母源mRNA。基因表达谱分析表明,在母源-合子转变过程中,这些mRNA中有一部分会经历Aub依赖的去稳定化。令人惊讶的是,Aub依赖的不稳定mRNA编码生殖细胞决定因子。用一种无法结合piRNA的Aub突变体进行iCLIP,证实了Aub与mRNA的piRNA依赖性结合。piRNA与mRNA之间的碱基配对可诱导mRNA的切割和降解,这对胚胎发育至关重要。这些结果表明Aub和piRNA对母源mRNA有普遍调控作用,它们通过对编码生殖细胞决定因子的mRNA的降解和定位,在胚胎发育中发挥关键作用。