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Series GSE144620 Query DataSets for GSE144620
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
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.
 
Overall design m6A-Seq was performed in wild type and AlKBH5 over-expressed HEK cells.
 
Contributor(s) Wei J, Cui X, Qian Z, He C
Citation(s) 34048572
Submission date Jan 31, 2020
Last update date Jun 15, 2021
Contact name Xiaolong Cui
E-mail(s) xiaolong.cui@northwestern.edu
Organization name Northwestern University
Department Department of Preventive Medicine
Street address 680 N Lake Shore Drive
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (24)
GSM4292376 Alkbh5_KO_minus_Input1
GSM4292377 Alkbh5_KO_minus_Input2
GSM4292378 Alkbh5_KO_minus_IP1
Relations
BioProject PRJNA604206
SRA SRP246340

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Supplementary file Size Download File type/resource
GSE144620_Alkbh5_KO_minus_peak.bed.gz 337.2 Kb (ftp)(http) BED
GSE144620_Alkbh5_KO_plus_peak.bed.gz 368.4 Kb (ftp)(http) BED
GSE144620_Alkbh5_mut_minus_peak.bed.gz 353.8 Kb (ftp)(http) BED
GSE144620_Alkbh5_mut_plus_peak.bed.gz 386.3 Kb (ftp)(http) BED
GSE144620_vec_minus_peak.bed.gz 324.8 Kb (ftp)(http) BED
GSE144620_vec_plus_peak.bed.gz 183.8 Kb (ftp)(http) BED
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Raw data are available in SRA
Processed data are available on Series record

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