title: 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 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; The University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Shan
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; The University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Wu
authors.affiliation: The University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: The University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhwang@genetics.ac.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D008297:Male; D008540:Meiosis; D008938:Mitosis; D026723:Polyadenylation; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D016601:RNA-Binding Proteins
keywords: 3′UTR; Alternative polyadenylation; Germ cell; Mitosis to meiosis; RNA-binding protein