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Status |
Public on Apr 29, 2021 |
Title |
Post-translational Modification of RNA m6A Demethylase ALKBH5 Regulates ROS-induced DNA Damage Response |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m6A levels that protect genomic integrity of cells in response to ROS.
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Overall design |
m6A-Seq was performed in wild type and AlKBH5 over-expressed HEK cells.
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Contributor(s) |
Wei J, Cui X, Qian Z, He C |
Citation(s) |
34048572 |
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Submission date |
Jan 31, 2020 |
Last update date |
Jun 15, 2021 |
Contact name |
Xiaolong Cui |
E-mail(s) |
xiaolong.cui@northwestern.edu
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Organization name |
Northwestern University
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Department |
Department of Preventive Medicine
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Street address |
680 N Lake Shore Drive
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City |
Chicago |
State/province |
IL |
ZIP/Postal code |
60611 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (24)
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Relations |
BioProject |
PRJNA604206 |
SRA |
SRP246340 |