Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response

Yu, Fang; Wei, Jiangbo; Cui, Xiaolong; Yu, Chunjie; Ni, Wei; Bungert, Jörg; Wu, Lizi; He, Chuan; Qian, Zhijian

doi:10.1093/nar/gkab415

Cited by 138 publications

(130 citation statements)

References 80 publications

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“…Interestingly, our study indicated that m6A demethylase ALKBH5 overexpression could curb cell proliferation by decreasing the protein expression of CyclinD1. However, ALKBH5 overexpression had no effect on cell apoptosis, which was inconsistent with a recent study [ 46 ]. We considered that this inconsistency was caused by the environment and cell lines.…”

Section: Discussioncontrasting

confidence: 98%

Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

Zhang

Cao

et al. 2021

Epigenetics & Chromatin

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Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Our previous study has found that ethionine inhibits cell viability by disrupting the balance between proliferation and apoptosis, and preventing neural stem cells from differentiating into neurons and astrocytes. However, how ethionine participates in the pathogenesis of neural tube development through N6-methyladenosine (m6A) modification remains unknown. This study aims to investigate METTL3- and ALKBH5-mediated m6A modification function and mechanism in NTDs. Herein, our results demonstrate that SAM play not only a compensatory role, it also leads to changes of m6A modification in neural tube development and regulation. Additionally, these data implicate that METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/β-catenin signaling pathway. Significantly, overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis. This research reveals an important role of SAM in development of NTDs, providing a good theoretical basis for further research on NTDs. This finding represents a novel epigenetic mechanism underlying that the m6A modification has profound and lasting implications for neural tube development.

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Section: Discussioncontrasting

confidence: 98%

Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

Zhang

Cao

et al. 2021

Epigenetics & Chromatin

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“…Furthermore, phosphorylated ALKBH5 further promotes the interaction between ALKBH5 and small ubiquitin-related modifier (SUMO)ylated E2 UBC9. At the same time, the ERK/JNK/ALKBH5 PTM/m6A axis was activated in hematopoietic stem/progenitor cells (HSPCs), which also contributed to maintaining stable genomic integrity and thereby participated in the DNA damage response ( Yu et al, 2021 ). In addition, in other studies, ALKBH5 is closely associated with sentrin/SUMO-specific proteases 1 and 3 (SENP1 and SENP3) under oxidative stress ( Xu et al, 2008 ; Huang et al, 2009 ; Wang et al, 2012 ).…”

Section: Atherosclerosis and The M6a Ribonucleic Acid Modificationmentioning

confidence: 99%

The Role of m6A Ribonucleic Acid Modification in the Occurrence of Atherosclerosis

Cui

Zhang

et al. 2021

Front. Genet.

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The N6-methyladenosine (m6A) modification is the most abundant epitranscriptomic modification in eukaryotic messenger RNA (mRNA). The m6A modification process is jointly regulated by various enzymes and proteins, such as methyltransferases, demethylases and related m6A-binding proteins. The process is dynamic and reversible, and it plays an essential role in mRNA metabolism and various biological activities. Recently, an increasing number of researchers have confirmed that the onset and development of many diseases are closely associated with the molecular biological mechanism of m6A RNA methylation. This study focuses on the relationship between m6A RNA modification and atherosclerosis (AS). It thoroughly summarizes the mechanisms and processes of m6A RNA modification in AS-related cells and the relationships between m6A RNA modification and AS risk factors, and it provides a reference for exploring new targets for the early diagnosis and treatment of AS.

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“…It has been reported that m6A modification in RNA is an early step of the DNA damage response ( 40 , 41 , 42 , 43 ). For example, METTL3/14 and FTO transiently and dynamically regulate m6A modification at DNA damage sites and then recruit Pol κ to facilitate DNA repair following UV exposure ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

m6A demethylation of cytidine deaminase APOBEC3B mRNA orchestrates arsenic-induced mutagenesis

Gao

Feng

et al. 2022

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response

Cited by 138 publications

References 80 publications

Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

The Role of m6A Ribonucleic Acid Modification in the Occurrence of Atherosclerosis

m6A demethylation of cytidine deaminase APOBEC3B mRNA orchestrates arsenic-induced mutagenesis

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