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Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis
Abstract: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 30-processing machinery to generate diverse 30 UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 30 UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 30 UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 30-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 30 UTRs of 30-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.
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