Genomics

Dataset Information

33

Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in Cell Nucleus and Cytoplasm


ABSTRACT: 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. 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

INSTRUMENT(S): Illumina HiSeq 4000 (Mus musculus)

ORGANISM(S): Mus musculus  

SUBMITTER: zhike lu  

PROVIDER: GSE106395 | GEO | 2018-09-14

REPOSITORIES: GEO

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Publications

Differential m<sup>6</sup>A, m<sup>6</sup>A<sub>m</sub>, and m<sup>1</sup>A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm.

Wei Jiangbo J   Liu Fange F   Lu Zhike Z   Fei Qili Q   Ai Yuxi Y   He P Cody PC   Shi Hailing H   Cui Xiaolong X   Su Rui R   Klungland Arne A   Jia Guifang G   Chen Jianjun J   He Chuan C  

Molecular cell 20180906 6


FTO, the first RNA demethylase discovered, mediates the demethylation of internal N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) and N<sup>6</sup>, 2-O-dimethyladenosine (m<sup>6</sup>A<sub>m</sub>) at the +1 position from the 5' cap in mRNA. Here we demonstrate that the cellular distribution of FTO is distinct among different cell lines, affecting the access of FTO to different RNA substrates. We find that FTO binds multiple RNA species, including mRNA, snRNA, and tRNA, and can demethylate inte  ...[more]

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