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Updated: Jun 12, 2025
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Published on: April 21, 2022
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Modulation of m6A RNA modification by DAP3 in cancer cells
Jian Han1, Yangyang Song1, Jinghe Xie1
1Cancer Science Institute of Singapore, 8, Singapore 117599, Singapore.
Summary
Death associated protein 3 (DAP3) maintains cancer m6A RNA methylation by facilitating METTL3 binding and increasing S-adenosylmethionine (SAM) levels. DAP3 acts as an RNA-binding protein and tumor promoter, impacting cancer transcriptomes.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- N6-methyladenosine (m6A) RNA methylation is a critical epigenetic modification influencing RNA metabolism and cancer progression.
- Cellular m6A levels depend on RNA accessibility to methyltransferases and the availability of the methyl donor, S-adenosylmethionine (SAM).
Purpose of the Study:
- To investigate the role of death associated protein 3 (DAP3) in regulating m6A RNA methylation and its impact on cancer development.
- To elucidate the mechanisms by which DAP3 influences m6A levels and tumorigenesis.
Main Methods:
- Investigated DAP3's interaction with m6A target regions and its effect on METTL3 binding.
- Analyzed DAP3's role in MAT2A gene splicing and its influence on cellular SAM levels.
- Assessed the impact of DAP3 silencing and MAT2A overexpression on tumorigenesis in cancer cells.
Main Results:
- DAP3 directly binds to m6A target regions, enhancing METTL3 binding and facilitating m6A modification.
- DAP3 promotes MAT2A pre-mRNA splicing, leading to increased MAT2A protein, cellular SAM, and global m6A levels.
- Silencing DAP3 inhibits tumorigenesis, an effect that can be reversed by overexpressing MAT2A.
Conclusions:
- DAP3 plays a significant role in preserving m6A RNA methylation levels in cancer cells through dual mechanisms.
- DAP3 functions as an RNA-binding protein and a tumor promoter, influencing RNA processing, splicing, and m6A modification in cancer transcriptomes.
- Targeting DAP3 may offer a therapeutic strategy for cancer, potentially by modulating m6A regulation.
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