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| Status |
Public on Sep 14, 2018 |
| Title |
Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in Cell Nucleus and Cytoplasm |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
FTO, the first RNA demethylase discovered, mediates the demethylation of N6-methyladenosine (m6A), installed internally on messenger RNA, and N6,2′-O-dimethyladenosine (m6Am), occurring at the +1 position from the 5’ cap. Despite extensive recent research on FTO, its physiological impact on cellular processes has yet to be fully elucidated. Here, we demonstrate that the cellular distribution of FTO is distinct among different cell lines, which critically affects the access of FTO to different RNA substrates. FTO binds multiple RNA substrates, including mRNA, U6 RNA, and tRNA. It mainly targets internal m6A when located in the cell nucleus and preferentially demethylates m6Am when residing in the cytoplasm. The expression levels of transcripts containing internal m6A are associated with the alteration of the FTO more so than transcripts containing m6Am. We also discover that N1-methyladenosine (m1A) in tRNA is a main substrate of FTO, with the FTO-catalyzed demethylation of target tRNAs repressing protein synthesis. Collectively, FTO-mediated RNA demethylation affects both mRNA level and translation through distinct pathways.
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| Overall design |
Profile the binding RNA of ALKBH1 by CLIP-seq in 3T3-L1 cells transfected with FLAG-tagged FTO. RNA-seq in HeLa cells transfected with FTO siRNA or control siRNA
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| Contributor(s) |
Lu Z, Liu F, Wei J, He C |
| Citation(s) |
30197295 |
| Submission date |
Nov 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
zhike lu |
| E-mail(s) |
zhikelu@gmail.com
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| Organization name |
University of Chicago
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| Department |
department of chemistry
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| Street address |
5801 South Ellis Avenue
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60637 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA416710 |
| SRA |
SRP123324 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE106395_RAW.tar |
10.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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