Aubergine iCLIP reveals direct regulation of mRNAs involved in germ cell development by piRNAs in the early embryo

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 undergoes 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 that binding of Aub to mRNAs is piRNA dependent. Base-pairing between piRNAs and mRNAs can induce mRNA cleavage and decay that are essential for embryonic development. These results reveal a general regulation of maternal mRNAs by Aub and piRNAs, which plays a key developmental role in the embryo, by mediating decay and localization of mRNAs encoding germ cell determinants. Overall design: We used Aub iCLIP (individual-nucleotide resolution UV cross-linking and immunoprecipitation) to identify RNAs interacting with Aub in 0-2h-Drosophila embryo