{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:55:18Z","timestamp":1787907318385,"version":"build-2784847793"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["1908085MC97"],"award-info":[{"award-number":["1908085MC97"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2008085MC85"],"award-info":[{"award-number":["2008085MC85"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Fund of State Key Laboratory of Genetic Resources and Evolution","award":["GREKF18-16"],"award-info":[{"award-number":["GREKF18-16"]}]},{"name":"Open Foundation of State Key Laboratory of Agrobiotechnology","award":["2018SKLAB6-3"],"award-info":[{"award-number":["2018SKLAB6-3"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31802059"],"award-info":[{"award-number":["31802059"]}],"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":["31902226"],"award-info":[{"award-number":["31902226"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hefei Innovation and Entrepreneurship Support Plan for Returnee Scholar","award":["03082009"],"award-info":[{"award-number":["03082009"]}]},{"name":"Anhui Provincial Innovation and Entrepreneurship Support Plan for Returnee Scholar","award":["2020LCX015"],"award-info":[{"award-number":["2020LCX015"]}]},{"name":"National Institute of Child Health and Development"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD095371"],"award-info":[{"award-number":["HD095371"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>N6-methyladenosine (m6A) catalyzed by METTL3 regulates the maternal-to-zygotic transition in zebrafish and mice. However, the role and mechanism of METTL3-mediated m6A methylation in blastocyst development remains unclear. Here, we show that METTL3-mediated m6A methylation sustains porcine blastocyst development via negatively modulating autophagy. We found that reduced m6A levels triggered by METTL3 knockdown caused embryonic arrest during morula-blastocyst transition and developmental defects in trophectoderm cells. Intriguingly, overexpression of METTL3 in early embryos resulted in increased m6A levels and these embryos phenocopied METTL3 knockdown embryos. Mechanistically, METTL3 knockdown or overexpression resulted in a significant increase or decrease in expression of ATG5 (a key regulator of autophagy) and LC3 (an autophagy marker) in blastocysts, respectively. m6A modification of ATG5 mRNA mainly occurs at 3\u2019UTR, and METTL3 knockdown enhanced ATG5 mRNA stability, suggesting that METTL3 negatively regulated autophagy in an m6A dependent manner. Furthermore, single-cell qPCR revealed that METTL3 knockdown only increased expression of LC3 and ATG5 in trophectoderm cells, indicating preferential inhibitory effects of METTL3 on autophagy activity in the trophectoderm lineage. Importantly, autophagy restoration by 3MA (an autophagy inhibitor) treatment partially rescued developmental defects of METTL3 knockdown blastocysts. Taken together, these results demonstrate that METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development.<\/jats:p>","DOI":"10.1093\/biolre\/ioab022","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T15:18:02Z","timestamp":1613661482000},"page":"1008-1021","source":"Crossref","is-referenced-by-count":32,"title":["METTL3-mediated m6A methylation negatively modulates autophagy to support porcine blastocyst development\u2021"],"prefix":"10.1093","volume":"104","author":[{"given":"Zubing","family":"Cao","sequence":"first","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ning","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Gao","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengteng","family":"Xu","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Ma","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yu","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G","family":"Knott","sequence":"additional","affiliation":[{"name":"Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anucha","family":"Sathanawongs","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, 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