Differential MA, MA, and MA Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Sep 11

PMID 30197295

Citations 393

Authors

Jiangbo Wei

Fange Liu

Zhike Lu

Qili Fei

Yuxi Ai

P Cody He

Hailing Shi

Xiaolong Cui

Rui Su

Arne Klungland

Guifang Jia

Jianjun Chen

Chuan He

Affiliations

Soon will be listed here.

Abstract

FTO, the first RNA demethylase discovered, mediates the demethylation of internal N-methyladenosine (mA) and N, 2-O-dimethyladenosine (mA) 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 internal mA and cap mA in mRNA, internal mA in U6 RNA, internal and cap mA in snRNAs, and N-methyladenosine (mA) in tRNA. FTO-mediated demethylation has a greater effect on the transcript levels of mRNAs possessing internal mA than the ones with cap mA in the tested cells. We also show that FTO can directly repress translation by catalyzing mA tRNA demethylation. Collectively, FTO-mediated RNA demethylation occurs to mA and mA in mRNA and snRNA as well as mA in tRNA.

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