Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Interaction between the N-methyladenosine (mA) methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit mA on various types of RNAs. It remains to be uncovered whether there is spatial control of mA deposition on different types of RNAs. Here, through genome-wide CRISPR-Cas9 screening in the A549 cell line, we find that H3K27ac acetylase p300-mediated METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Consistently, p300 catalyzing the acetylation of METTL3 specifically occurs on H3K27ac-marked chromatin. Disruptive mutations on METTL3 acetylation sites selectively promote the mA of chromatin-associated RNAs from p300-bound enhancers and promoters marked by H3K27ac, resulting in transcription inhibition of ferroptosis-inhibition-related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes ferroptosis in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of mA on enhancer and promoter RNAs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molcel.2025.02.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NUTM2A-AS1 as a potential key regulator in cancer: unraveling its ceRNA networks and impact on tumor biology.
Eur J Med Res
September 2025
Dentistry School, Shiraz University of Medical Sciences, Shiraz, Iran.
NUTM2A-AS1 is an emerging long noncoding RNA (lncRNA) that has garnered significant attention due to its multifaceted roles in cancer biology. As a member of the ceRNA network, NUTM2A-AS1 modulates gene expression by sequestering microRNAs, thereby influencing key oncogenic pathways. This review aims to provide a comprehensive overview of the current understanding of NUTM2A-AS1 in the development, progression, and metastasis of various cancers, including gastric cancer, hepatocellular carcinoma, neuroblastoma, colorectal cancer, glioma, lung adenocarcinoma, prostate cancer, and renal cell carcinoma.
View Article and Find Full Text PDFH3K27ac Is Essential for Human Naive Pluripotency Modulated by m6A-Driven EP300 Expression.
Adv Sci (Weinh)
August 2025
Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Af
Human pluripotent stem cells (hPSCs) can transition between primed and naive states, each defined by unique epigenetic features crucial for early human development. However, the precise regulatory mechanisms of these transitions, particularly involving the roles of H3K27ac and m6A modifications, remain unclear. Here, it is revealed that H3K27ac is essential for establishment of human naive pluripotency.
View Article and Find Full Text PDFAcetylation of METTL3: A negative regulator of mA deposition on chromatin-associated regulatory RNAs.
Mol Cell
April 2025
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. Electronic address:
In this issue, Huang et al. report the acetylation of METTL3 as a negative regulator of mA deposition of chromatin-associated regulatory RNAs from enhancers and promoters. This acetylation is mediated by p300 and positively regulated by PAK2.
View Article and Find Full Text PDFSpatial control of mA deposition on enhancer and promoter RNAs through co-acetylation of METTL3 and H3K27 on chromatin.
Mol Cell
April 2025
Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, C
Interaction between the N-methyladenosine (mA) methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit mA on various types of RNAs. It remains to be uncovered whether there is spatial control of mA deposition on different types of RNAs. Here, through genome-wide CRISPR-Cas9 screening in the A549 cell line, we find that H3K27ac acetylase p300-mediated METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14.
View Article and Find Full Text PDF3-Acetyldeoxynivalenol induces pyroptosis in leydig cells via METTL3-mediated N6-methyladenosine modification of NLRP3.
Ecotoxicol Environ Saf
January 2025
Department of Urology, The Fifth People's Hospital of Shanghai, Fudan University, 200240, China.
3-acetyldeoxynivalenol (3-ADON), an acetylated derivative of deoxynivalenol, is a prevalent contaminant found in food products contaminated with mycotoxins. While the toxicological effects of 3-ADON on human and animal health are well-documented, its specific impact on the reproductive system remains underexplored. In this study, we comprehensively examined the toxicological effects of 3-ADON on TM3 Leydig cells through both in vivo and in vitro experimental models.
View Article and Find Full Text PDF