Evidence map›Paper›PMID 33590832›Full record

ArticleBiology of reproduction2021

METTL3-mediated m6A methylation negatively modulates autophagy to support porcine blastocyst development‡.

Zubing Cao, Ling Zhang, Renyun Hong, Yunsheng Li, Yiqing Wang, Xin Qi, Wei Ning, Di Gao, Tengteng Xu, Yangyang Ma and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Biology of reproduction, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 29 citations in OpenAlex.

  1. Ncl1-dependent mPlant communications · 2026
    Article
  2. Emerging roles of mJournal of assisted reproduction and genetics · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. mCell · 2025
    Article
  7. Article
  8. Review
  9. Review
  10. mActa biochimica et biophysica Sinica · 2023
    Review
  11. Article
  12. Review
  13. Article
  14. Article
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  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 3 countries.

Zubing CaoAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Ling ZhangAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Renyun HongDepartment of Reproductive Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Yunsheng LiAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Yiqing WangAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Xin QiAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Wei NingAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Di GaoAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Tengteng XuAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Yangyang MaAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Tong YuAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Jason G KnottDevelopmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI, USA.
Anucha SathanawongsDepartment of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand.
Yunhai ZhangAnhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Anhui Agricultural University · CNChiang Mai University · THMichigan State University · USZhongda Hospital Southeast University · CN

Funding

Mechanisms of trophoblast lineage formation: Impact on postimplantation placental developmentR01HD095371 · NICHD · MICHIGAN STATE UNIVERSITY · PI KNOTT, JASON GLENN · 2018 to 2022
$1.6M
NICHD NIH HHS R01 HD095371
6 · The paper itself

Abstract

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'UTR, 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.

Indexed as

AnimalsAutophagyBlastocystMembrane GlycoproteinsMethyltransferasesNerve Tissue ProteinsSus scrofaMembrane GlycoproteinsMethyltransferasesNerve Tissue ProteinsATG5autophagyblastocystm6A methylationMETTL3

Identifiers

PMID33590832
PMCPMC8111235
OpenAlexW3131581930

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.