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Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.<\/jats:p>","DOI":"10.1093\/nar\/gkab155","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T12:24:04Z","timestamp":1614342244000},"page":"3796-3813","source":"Crossref","is-referenced-by-count":81,"title":["MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of <i>GNRH1<\/i> mRNA in mammalian puberty"],"prefix":"10.1093","volume":"49","author":[{"given":"Chuanyin","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"},{"name":"Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianting","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingrun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Juvenile Endocrinology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-239X","authenticated-orcid":false,"given":"Ronggui","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"},{"name":"Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200031, China"},{"name":"Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease, Institute (BCBDI), Shenzhen Institutes of Advanced Technology, 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