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PMID: 22002720 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.

Nature chemical biology ·Vol. 7 ·No. 12 ·2011-10-16 ·Pages 885-7

Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C

Abstract

We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m(6)A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m(6)A in mRNA, whereas overexpression of FTO resulted in decreased amounts of m(6)A in human cells. We further show the partial colocalization of FTO with nuclear speckles, which supports the notion that m(6)A in nuclear RNA is a major physiological substrate of FTO.

MeSH Terms

Adenosine/analogs & derivatives,metabolism Alpha-Ketoglutarate-Dependent Dioxygenase FTO Cell Nucleus/genetics,metabolism HeLa Cells Humans Methylation Obesity Oxidation-Reduction Proteins/genetics,metabolism RNA, Messenger/chemistry,metabolism Substrate Specificity

Chemicals

Proteins RNA, Messenger N-methyladenosine Alpha-Ketoglutarate-Dependent Dioxygenase FTO FTO protein, human Adenosine

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

Jia Guifang

Department of Chemistry, University of Chicago, Chicago, Illinois, USA.

Fu Ye

Zhao Xu

Dai Qing

Zheng Guanqun

Yang Ying

Yi Chengqi

Lindahl Tomas

Pan Tao

Yang Yun-Gui

He Chuan

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Article Info

Journal

Nature chemical biology

Abbr.

Nat Chem Biol

ISSN

1552-4469

DOI

10.1038/nchembio.687

Published

2011-10-16

Epub

2011-00-16

Pages

885-7

Language

English

Region

United States

NLM ID

101231976

PMCID

PMC3218240

Subset

Grants

NIGMS NIH HHS · R01 GM071440-07 · United States

NIGMS NIH HHS · R01 GM088599 · United States

NIGMS NIH HHS · R01 GM071440 · United States

NIGMS NIH HHS · R01 GM071440-06 · United States

NIGMS NIH HHS · GM088599 · United States

NIGMS NIH HHS · GM071440 · United States

Corrections

ErratumIn

External Links

PubMed source DOI: 10.1038/nchembio.687 PMC Full Text View journal details

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N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.

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