{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:03:23Z","timestamp":1790741003043,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31890781"],"award-info":[{"award-number":["31890781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930031"],"award-info":[{"award-number":["31930031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91949108"],"award-info":[{"award-number":["91949108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The CCR4\u2010NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6\/6L and CNOT7\/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. <jats:italic>Cnot7<\/jats:italic> knockout male mice have been reported to be infertile. In this study, viable <jats:italic>Cnot6<\/jats:italic>\/<jats:italic>6l<\/jats:italic> double knockout mice are constructed, and the males are fertile. These results indicate that CNOT7 has CNOT6\/6L\u2010independent functions in vivo. It is also demonstrated that CNOT4 is required for post\u2010implantation embryo development and meiosis progression during spermatogenesis. Conditional knockout of <jats:italic>Cnot4<\/jats:italic> in male germ cells leads to defective DNA damage repair and homologous crossover between X and Y chromosomes. CNOT4 functions as a previously unrecognized mRNA adaptor of CCR4\u2010NOT by targeting mRNAs to CNOT7 for deadenylation of poly(A) tails, thereby mediating the degradation of a subset of transcripts from the zygotene to pachytene stage. The mRNA removal promoted by the CNOT4\u2010regulated CCR4\u2010NOT complex during the zygotene\u2010to\u2010pachytene transition is crucial for the appropriate expression of genes involved in the subsequent events of spermatogenesis, normal DNA double\u2010strand break repair during meiosis, efficient crossover between X and Y chromosomes, and ultimately, male fertility.<\/jats:p>","DOI":"10.1002\/advs.202003636","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T08:47:53Z","timestamp":1615884473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The CNOT4 Subunit of the CCR4\u2010NOT Complex is Involved in mRNA Degradation, Efficient DNA Damage Repair, and XY Chromosome Crossover during Male Germ Cell Meiosis"],"prefix":"10.1002","volume":"8","author":[{"given":"Xing\u2010Xing","family":"Dai","sequence":"first","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Hui","family":"Gu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Science Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yin","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of USTC Hefei National Laboratory for Physical Sciences at Microscale School of Basic Medical Sciences Division of Life Sciences and Medicine CAS Center for Excellence in Molecular Cell Science University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITIC\u2010XIANGYA  Changsha 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Hua","family":"Shi","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of USTC Hefei National Laboratory for Physical Sciences at Microscale School of Basic Medical Sciences Division of Life Sciences and Medicine CAS Center for Excellence in Molecular Cell Science University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Qian","family":"Sha","sequence":"additional","affiliation":[{"name":"Fertility Preservation Laboratory Reproductive Medicine Center Guangdong Second Provincial General Hospital  Guangzhou 510317 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-4724","authenticated-orcid":false,"given":"Heng\u2010Yu","family":"Fan","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Biosystems Homeostasis &amp; Protection and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20120074"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2011.09.033"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-46503-6_13"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-02-0146"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.05.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.05.033"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600051"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2012.667214"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.3.355"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090500"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84051-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28046"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.007"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1769209"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.384719"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07957.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26576-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899333"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201800084"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3204"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjw023"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.13.5808-5820.2004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-110711-155423"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016634"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06593.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195774"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31805"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2327-4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-018-0128-1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23318"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.055"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-018-0074-y"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11346-y"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3573"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/151.4.1569"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007439"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11094-z"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.320952.118"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2311"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130211"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1111"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201949956"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22024"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10845"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2015.1093709"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2012.12.002"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201540828"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033558"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.41"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22463"},{"key":"e_1_2_8_51_1","first-page":"55378","volume":"129","author":"Dia F.","year":"2017","journal-title":"J. Vis. Exp."},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1159\/000129818"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.006"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202003636","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202003636","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202003636","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:46:57Z","timestamp":1759787217000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202003636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/advs.202003636"],"URL":"https:\/\/doi.org\/10.1002\/advs.202003636","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"assertion":[{"value":"2020-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2003636"}}