title: A MAPK cascade couples maternal mRNA translation and degradation to meiotic cell cycle progression in mouse oocytes.
abstract: Mammalian oocyte maturation depends on the translational activation of stored maternal mRNAs upon meiotic resumption. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a key oocyte factor that regulates maternal mRNA translation. However, the signal that triggers CPEB1 activation at the onset of mammalian oocyte maturation is not known. We provide evidence that a mitogen-activated protein kinase (MAPK) cascade couples maternal mRNA translation to meiotic cell cycle progression in mouse oocytes by triggering CPEB1 phosphorylation and degradation. Mutations of the phosphorylation sites or ubiquitin E3 ligase binding sites in CPEB1 have a dominant-negative effect in oocytes, and mimic the phenotype of ERK1/2 knockout, by impairing spindle assembly and mRNA translation. Overexpression of the CPEB1 downstream translation activator DAZL in ERK1/2-deficient oocytes partially rescued the meiotic defects, indicating that ERK1/2 is essential for spindle assembly, metaphase II arrest and maternal-zygotic transition (MZT) primarily by triggering the translation of key maternal mRNAs. Taken together, ERK1/2-mediated CPEB1 phosphorylation/degradation is a major mechanism of maternal mRNA translational activation, and is crucial for mouse oocyte maturation and MZT.
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Sha
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Dai
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: Institute of Aging Research, Hangzhou Normal University, Hangzhou 311121, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China hyfan@zju.edu.cn 21118326@zju.edu.cn.|Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Yin-Li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Life Sciences Institute, Zhejiang University, Hangzhou 310058, China hyfan@zju.edu.cn 21118326@zju.edu.cn.
authors.forename: Heng-Yu
authors.identifier: 0000-0003-4544-4724
authors.initials: HY
authors.lastname: Fan
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics; D005260:Female; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D009866:Oogenesis; D010766:Phosphorylation; D020871:RNA Stability; D023121:RNA, Messenger, Stored / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D015053:Zygote / Q000166:cytology / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C485928:Btg4 protein, mouse; D018797:Cell Cycle Proteins; C490387:Cpeb1 protein, mouse; C508515:DAZL protein, mouse; D023121:RNA, Messenger, Stored; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors
keywords: Female fertility; MAPK cascade; Maternal-zygotic transition; Meiosis; Oocyte maturation; mRNA translation