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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
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N6-methyladenosine regulates ATM expression and downstream signaling
Xiaoyue Zhang1,2,3, Peishan Liu2,3, Xiang Zheng2,3,4
1Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Journal of Cancer
|November 3, 2021
Summary
This study reveals that N6-methyladenosine (m6A) epigenetically modifies the ATM gene, crucial for DNA damage response. METTL3 and YTHDF1 influence ATM expression, impacting cellular responses and potentially driving oncogenesis.
Area of Science:
- Epigenetics and RNA Modifications
- DNA Damage Response Pathways
- Cancer Biology
Background:
- N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes, regulating gene expression and biological processes.
- ATM (Ataxia-Telangiectasia Mutated) is a critical protein kinase central to the DNA damage response (DDR).
Purpose of the Study:
- To investigate the novel role of m6A epigenetic modification on the ATM gene.
- To elucidate the regulatory mechanisms of m6A modifiers (METTL3, FTO) and readers (YTHDFs, eIF3A) on ATM expression and function.
- To explore the implications of ATM m6A modification in oncogenesis.
Main Methods:
- Identification of ATM as an m6A-modified gene.
- Analysis of the opposing regulatory roles of METTL3 (m6A writer) and FTO (m6A eraser) on ATM expression.
- Investigation of m6A readers (YTHDFs, eIF3A) in suppressing ATM expression at the post-transcriptional level.
- Assessment of the oncogenic potential linked to METTL3 and YTHDF1 in ATM modulation.
Main Results:
- ATM was confirmed as a gene directly modified by m6A.
- METTL3 and FTO demonstrated opposing effects on ATM expression and its downstream signaling.
- m6A readers YTHDFs and eIF3A were found to suppress ATM expression post-transcriptionally.
- METTL3 and YTHDF1 exhibited oncogenic potential through ATM modulation.
Conclusions:
- This study establishes ATM as an m6A-modified gene, linking epigenetic regulation to the DNA damage response.
- METTL3 destabilizes ATM via m6A modification, thereby impacting the DNA damage response.
- The findings reveal a novel layer of regulation for ATM and highlight its role in oncogenesis.
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