N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO

By Guifang Jia, Ye Fu, Xu Zhao, Qing Dai, G. Zheng, Ying Yang, C. Yi, Tomas Lindahl, Tao Pan, Yun-Gui Yang and 1 more. Nature Chemical Biology, 2011

759 citations recorded by the source corpus.

We report here that FTO (fat mass and obesity-associated protein) exhibits efficient oxidative demethylation activity of abundant N6-methyladenosine (m6A) residues in RNA in vitro. FTO knockdown with siRNA led to an increased level of m6A in mRNA, whereas overexpression of FTO resulted in a decreased level of m6A in human cells. We further show that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f50977b36459d29ede793f51ffa99433d69d6e8f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Chuan He
2. Pedro J. Batista
3. Howard Y. Chang
4. Y. Yue
5. Jianzhao Liu
6. Kate D. Meyer
7. Samie R. Jaffrey
8. P. He

In Molecular Biology

1. Chuan He
2. Samie R. Jaffrey
3. P. He
4. Kate D. Meyer
5. Hailing Shi
6. Pedro J. Batista
7. Jianzhao Liu
8. Howard Y. Chang

Citations in the corpus

• The potential role of RNA N6-methyladenosine in Cancer progression (2020, background): “The first m6A demethylase, FTO, was discovered in 2011 [6].”
• RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation (2015, positive): “Whether and how WTAP regulates alternative splicing in an m6A-dependent manner have yet to be systematically explored. m6A erasers in mammals FTO is the first identified demethylase that oxidatively reverses m6A to adenosine inmRNA (Jia et al. 2011).”
• m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer (2018, positive): “This modification is reversible 3 , and its biological effects are mostly mediated through “writer,” “eraser,” and “reader” proteins 1,2 .”
• Rethinking m6A Readers, Writers, and Erasers (2017, background): “This study proposed that FTO, an enzyme previously associated with human obesity, is an m6A demethylase (Jia et al. 2011).”
• m6A RNA modification controls cell fate transition in mammalian embryonic stem cells (2014, methodology): “Two members of the alpha ketoglutarate-dependent dioxygenases protein family, fat-mass and obesity associated protein (FTO) and ALKBH5 have been shown to act as m6A demethylases (Jia et al., 2011; Zheng et al., 2013).”