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


: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.


Nat Chem Biol


Nature chemical biology


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




Has Abstract


2011-10-16 00:00:00














  • Membranes: first steps to rafts?

    abstract::Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membrane...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Silvius JR

    更新日期:2012-09-01 00:00:00

  • Mammalian circadian signaling networks and therapeutic targets.

    abstract::Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coor...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审


    authors: Liu AC,Lewis WG,Kay SA

    更新日期:2007-10-01 00:00:00

  • A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis.

    abstract::We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl transfe...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Gisin J,Schneider A,Nägele B,Borisova M,Mayer C

    更新日期:2013-08-01 00:00:00

  • Development of a covalent inhibitor of gut bacterial bile salt hydrolases.

    abstract::Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Adhikari AA,Seegar TCM,Ficarro SB,McCurry MD,Ramachandran D,Yao L,Chaudhari SN,Ndousse-Fetter S,Banks AS,Marto JA,Blacklow SC,Devlin AS

    更新日期:2020-03-01 00:00:00

  • Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine.

    abstract::Designing selective inhibitors of proteases has proven problematic, in part because pharmacophores that confer potency exploit the conserved catalytic apparatus. We developed a fundamentally different approach by designing irreversible inhibitors that target noncatalytic cysteines that are structurally unique to a tar...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Hagel M,Niu D,St Martin T,Sheets MP,Qiao L,Bernard H,Karp RM,Zhu Z,Labenski MT,Chaturvedi P,Nacht M,Westlin WF,Petter RC,Singh J

    更新日期:2011-01-01 00:00:00

  • N-terminal domains mediate [2Fe-2S] cluster transfer from glutaredoxin-3 to anamorsin.

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    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Banci L,Ciofi-Baffoni S,Gajda K,Muzzioli R,Peruzzini R,Winkelmann J

    更新日期:2015-10-01 00:00:00

  • Metals induce transient folding and activation of the twister ribozyme.

    abstract::Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although mo...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Panja S,Hua B,Zegarra D,Ha T,Woodson SA

    更新日期:2017-10-01 00:00:00

  • The catalytic cycle of a thiamin diphosphate enzyme examined by cryocrystallography.

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    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Wille G,Meyer D,Steinmetz A,Hinze E,Golbik R,Tittmann K

    更新日期:2006-06-01 00:00:00

  • HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains.

    abstract::Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Yang ST,Kiessling V,Simmons JA,White JM,Tamm LK

    更新日期:2015-06-01 00:00:00

  • Structure and function of the bacterial decapping enzyme NudC.

    abstract::RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Höfer K,Li S,Abele F,Frindert J,Schlotthauer J,Grawenhoff J,Du J,Patel DJ,Jäschke A

    更新日期:2016-09-01 00:00:00

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    abstract::Methods for imaging and tracking single molecules conjugated with fluorescent probes, called single-molecule tracking (SMT), are now providing researchers with the unprecedented ability to directly observe molecular behaviors and interactions in living cells. Current SMT methods are achieving almost the ultimate spati...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审


    authors: Kusumi A,Tsunoyama TA,Hirosawa KM,Kasai RS,Fujiwara TK

    更新日期:2014-07-01 00:00:00

  • Structural landscape of isolated agonist-binding domains from single AMPA receptors.

    abstract::AMPA receptors mediate fast excitatory neurotransmission by converting chemical signals into electrical signals, and thus it is important to understand the relationship between their chemical biology and their function. We used single-molecule fluorescence resonance energy transfer to examine the conformations explore...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Landes CF,Rambhadran A,Taylor JN,Salatan F,Jayaraman V

    更新日期:2011-03-01 00:00:00

  • Efficient genetic encoding of phosphoserine and its nonhydrolyzable analog.

    abstract::Serine phosphorylation is a key post-translational modification that regulates diverse biological processes. Powerful analytical methods have identified thousands of phosphorylation sites, but many of their functions remain to be deciphered. A key to understanding the function of protein phosphorylation is access to p...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Rogerson DT,Sachdeva A,Wang K,Haq T,Kazlauskaite A,Hancock SM,Huguenin-Dezot N,Muqit MM,Fry AM,Bayliss R,Chin JW

    更新日期:2015-07-01 00:00:00

  • Marine antifungal theonellamides target 3beta-hydroxysterol to activate Rho1 signaling.

    abstract::Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Here we report the mode of action of theonellamides, bicyclic peptides derived from marine sponges. We generated a chemical-genomic profile of theonellamide F using a collection of fission yeast strains in which each open...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Nishimura S,Arita Y,Honda M,Iwamoto K,Matsuyama A,Shirai A,Kawasaki H,Kakeya H,Kobayashi T,Matsunaga S,Yoshida M

    更新日期:2010-07-01 00:00:00

  • Chemical hijacking of auxin signaling with an engineered auxin-TIR1 pair.

    abstract::The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-b...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Uchida N,Takahashi K,Iwasaki R,Yamada R,Yoshimura M,Endo TA,Kimura S,Zhang H,Nomoto M,Tada Y,Kinoshita T,Itami K,Hagihara S,Torii KU

    更新日期:2018-03-01 00:00:00

  • Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases.

    abstract::Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Lauinger L,Li J,Shostak A,Cemel IA,Ha N,Zhang Y,Merkl PE,Obermeyer S,Stankovic-Valentin N,Schafmeier T,Wever WJ,Bowers AA,Carter KP,Palmer AE,Tschochner H,Melchior F,Deshaies RJ,Brunner M,Diernfellner A

    更新日期:2017-07-01 00:00:00

  • Unifying principles of bifunctional, proximity-inducing small molecules.

    abstract::Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these 'bifunction...

    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审


    authors: Gerry CJ,Schreiber SL

    更新日期:2020-04-01 00:00:00

  • Chemical phylogenetics of histone deacetylases.

    abstract::The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Bradner JE,West N,Grachan ML,Greenberg EF,Haggarty SJ,Warnow T,Mazitschek R

    更新日期:2010-03-01 00:00:00

  • Calcium Green FlAsH as a genetically targeted small-molecule calcium indicator.

    abstract::Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] su...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Tour O,Adams SR,Kerr RA,Meijer RM,Sejnowski TJ,Tsien RW,Tsien RY

    更新日期:2007-07-01 00:00:00

  • Discovery of a selective inhibitor of doublecortin like kinase 1.

    abstract::Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vi...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Ferguson FM,Nabet B,Raghavan S,Liu Y,Leggett AL,Kuljanin M,Kalekar RL,Yang A,He S,Wang J,Ng RWS,Sulahian R,Li L,Poulin EJ,Huang L,Koren J,Dieguez-Martinez N,Espinosa S,Zeng Z,Corona CR,Vasta JD,Ohi R,Sim T,K

    更新日期:2020-06-01 00:00:00

  • An intrinsically disordered entropic switch determines allostery in Phd-Doc regulation.

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    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Garcia-Pino A,De Gieter S,Talavera A,De Greve H,Efremov RG,Loris R

    更新日期:2016-07-01 00:00:00

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    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Leidecker O,Bonfiglio JJ,Colby T,Zhang Q,Atanassov I,Zaja R,Palazzo L,Stockum A,Ahel I,Matic I

    更新日期:2016-12-01 00:00:00

  • A reactivity-based probe of the intracellular labile ferrous iron pool.

    abstract::Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Spangler B,Morgan CW,Fontaine SD,Vander Wal MN,Chang CJ,Wells JA,Renslo AR

    更新日期:2016-09-01 00:00:00

  • Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges.

    abstract::Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most p...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Agarwal V,Blanton JM,Podell S,Taton A,Schorn MA,Busch J,Lin Z,Schmidt EW,Jensen PR,Paul VJ,Biggs JS,Golden JW,Allen EE,Moore BS

    更新日期:2017-05-01 00:00:00

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    journal_title:Nature chemical biology

    pub_type: 杂志文章,评审


    authors: Baldwin AJ,Kay LE

    更新日期:2009-11-01 00:00:00

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    abstract::The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Schmitt S,Montalbán-López M,Peterhoff D,Deng J,Wagner R,Held M,Kuipers OP,Panke S

    更新日期:2019-05-01 00:00:00

  • The radical SAM enzyme AlbA catalyzes thioether bond formation in subtilosin A.

    abstract::Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Flühe L,Knappe TA,Gattner MJ,Schäfer A,Burghaus O,Linne U,Marahiel MA

    更新日期:2012-02-26 00:00:00

  • Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans.

    abstract::The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Boland S,Schmidt U,Zagoriy V,Sampaio JL,Fritsche RF,Czerwonka R,Lübken T,Reimann J,Penkov S,Knölker HJ,Kurzchalia TV

    更新日期:2017-06-01 00:00:00

  • An orthogonalized platform for genetic code expansion in both bacteria and eukaryotes.

    abstract::In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNATrp) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Italia JS,Addy PS,Wrobel CJ,Crawford LA,Lajoie MJ,Zheng Y,Chatterjee A

    更新日期:2017-04-01 00:00:00

  • Light-based control of metabolic flux through assembly of synthetic organelles.

    abstract::To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...

    journal_title:Nature chemical biology

    pub_type: 杂志文章


    authors: Zhao EM,Suek N,Wilson MZ,Dine E,Pannucci NL,Gitai Z,Avalos JL,Toettcher JE

    更新日期:2019-06-01 00:00:00