Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis

In the sexually reproductive organisms, gametes are produced by meiosis following a limited mitotic amplification. However, the intrinsic program switching cells from mitotic to meiotic cycle is unclear. Alternative polyadenylation (APA) is a highly conserved means of gene regulation and is achieved by the RNA 3′-processing machinery to generate diverse 3′UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 3′UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 3′UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 3′-processing factors disrupted germline's progression to meiosis, indicative of APA's active role in this transition. An RNA-binding protein (RBP) Tut could directly bind 3′UTRs of 3′-processing factors whose expressions were repressed in the presence of Tut-containing complex. Further, we demonstrated that this RBP complex could execute the repression post-transcriptionally by recruiting CCR4/Twin of deadenylation complex. Thus, we propose that an RBP complex regulates the dynamic APA profile to promote the mitosis-to-meiosis transition.