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

Lingjuan Shan^{a, b, #},
Chan Wu^{a, b, #},
Di Chen^b,
Lei Hou^c,
Xin Li^a,
Lixia Wang^a,
Xiao Chu^{b, e},
Yifeng Hou^d,
Zhaohui Wang^{a
, ,}

a.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
b.
The University of Chinese Academy of Sciences, Beijing 100049, China
c.
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
d.
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
e.
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

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Corresponding author: E-mail address: zhwang@genetics.ac.cn (Zhaohui Wang)

These authors contributed equally to this study.

摘要

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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.
- Germ cell /
- Mitosis to meiosis /
- Alternative polyadenylation /
- RNA-binding protein /
- 3′UTR
These authors contributed equally to this study.
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