GSE108183
Dazl maintains proliferating germ cells through a network of polyA-proximal mRNA interactions [P6 iCLIP]
Dazl (deleted in azoospermia like) is a member of the DAZ family of germ cell-restricted RNA binding proteins required for gametogenesis from worm to human.  The direct RNA targets and functions of these essential proteins are poorly understood.  Here, we generated high-resolution, transcriptome-wide maps of Dazl-RNA interactions in mouse testes.  These maps provide important insights into the mechanism of Dazl recruitment to mRNA and reveal Dazl binding to thousands of mRNAs predominantly through sequence-specific interactions near the polyA tail.  Using transgenic mice and fluorescence activated cell sorting (FACS), we isolated DAZL knockout germ cells and used RNA-Seq to identify mRNAs sensitive to DAZL-ablation.  Intersecting the RNA-Seq and Dazl-RNA interaction datasets revealed that Dazl enhances expression of a subset of directly-bound transcripts, namely mRNAs for a network of essential cell cycle regulatory genes.  Collectively, our integrative analysis delineates a Dazl-dependent post-transcriptional gene regulatory program essential for mammalian germ cell maintenance. Overall design: Dazl iCLIP libraries generated from postnatal day 6 mouse testes (3 biological replicates)