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| Status |
Public on Jun 30, 2024 |
| Title |
Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation [MDA-MB-231-meRIPSeq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Here we show that nitric oxide (NO) is a potent inhibitor of FTO demethylase activity by directly binding to the catalytic iron center, which causes global m6A hypermethylation of mRNA in cells and results in gene-specific enrichment of m6A on mRNA of NO-regulated transcripts. Both cell culture and tumor xenograft models demonstrated that endogenous NO synthesis can regulate m6A-mRNA levels and transcriptional changes of m6A-associated genes. These results build a direct link between NO and m6A-mRNA regulation and reveal a novel signaling mechanism of NO as an endogenous regulator of the epitranscriptome.
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| Overall design |
With the observation that NO directly inhibits FTO demethylase activity and globally increases m6A-mRNA, we sought to decipher whether this was functionally associated with transcriptional changes in NO-regulated genes. First, we quantified changes in transcription by performing RNA-sequencing on samples from two cell lines treated chronically (10 days) with NO.
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| Citation missing |
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| Submission date |
Jun 30, 2023 |
| Last update date |
Jul 01, 2024 |
| Contact name |
Douglas D Thomas |
| E-mail(s) |
ddthomas@uic.edu
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| Phone |
312-996-6156
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| Organization name |
University of Illinois at Chicago
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| Department |
Pharmaceutical Sciences
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| Street address |
833 S. Wood Street, MC 781
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60612 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| GSM7526976 |
MDA-MB-231, Utb, Day 10, m6A |
| GSM7526977 |
MDA-MB-231, NOa, Day 10, INP |
| GSM7526978 |
MDA-MB-231, NOa, Day 10, m6A |
| GSM7526980 |
MDA-MB-231, NOb, Day 10, INP |
| GSM7526981 |
MDA-MB-231, NOb, Day 10, m6A |
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| This SubSeries is part of SuperSeries: |
| GSE236272 |
Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation |
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| Relations |
| BioProject |
PRJNA989609 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE236271_RAW.tar |
306.3 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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