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

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.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

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

doi

10.1038/nchembio.687

subject

Has Abstract

pub_date

2011-10-16 00:00:00

pages

885-7

issue

12

eissn

1552-4450

issn

1552-4469

pii

nchembio.687

journal_volume

7

pub_type

杂志文章
  • 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

    doi:10.1038/nchembio.798

    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

  • Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA.

    abstract::RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2228

    authors: Weldon C,Behm-Ansmant I,Hurley LH,Burley GA,Branlant C,Eperon IC,Dominguez C

    更新日期:2017-01-01 00:00:00

  • A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate.

    abstract::Serine is both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical pathway of glucose-derived serine synthesis, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step. Genetic loss of PHGDH is tox...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2070

    authors: Pacold ME,Brimacombe KR,Chan SH,Rohde JM,Lewis CA,Swier LJ,Possemato R,Chen WW,Sullivan LB,Fiske BP,Cho S,Freinkman E,Birsoy K,Abu-Remaileh M,Shaul YD,Liu CM,Zhou M,Koh MJ,Chung H,Davidson SM,Luengo A,Wang AQ,

    更新日期:2016-06-01 00:00:00

  • Light-activated chemical probing of nucleobase solvent accessibility inside cells.

    abstract::The discovery of functional RNAs that are critical for normal and disease physiology continues to expand at a breakneck pace. Many RNA functions are controlled by the formation of specific structures, and an understanding of each structural component is necessary to elucidate its function. Measuring solvent accessibil...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2548

    authors: Feng C,Chan D,Joseph J,Muuronen M,Coldren WH,Dai N,Corrêa IR Jr,Furche F,Hadad CM,Spitale RC

    更新日期:2018-03-01 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

    doi:10.1038/nchembio.2459

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

    更新日期:2017-10-01 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

    doi:10.1038/nchembio.492

    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

  • Mixture of new sulfated steroids functions as a migratory pheromone in the sea lamprey.

    abstract::The sea lamprey is an ancient, parasitic fish that invaded the Great Lakes a century ago, where it triggered the collapse of many fisheries. Like many fishes, this species relies on chemical cues to mediate key aspects of its life, including migration and reproduction. Here we report the discovery of a multicomponent ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio739

    authors: Sorensen PW,Fine JM,Dvornikovs V,Jeffrey CS,Shao F,Wang J,Vrieze LA,Anderson KR,Hoye TR

    更新日期:2005-11-01 00:00:00

  • SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate.

    abstract::Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show th...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-018-0129-x

    authors: Matyskiela ME,Couto S,Zheng X,Lu G,Hui J,Stamp K,Drew C,Ren Y,Wang M,Carpenter A,Lee CW,Clayton T,Fang W,Lu CC,Riley M,Abdubek P,Blease K,Hartke J,Kumar G,Vessey R,Rolfe M,Hamann LG,Chamberlain PP

    更新日期:2018-10-01 00:00:00

  • Nitric oxide activates TRP channels by cysteine S-nitrosylation.

    abstract::Transient receptor potential (TRP) proteins form plasma-membrane cation channels that act as sensors for diverse cellular stimuli. Here, we report a novel activation mechanism mediated by cysteine S-nitrosylation in TRP channels. Recombinant TRPC1, TRPC4, TRPC5, TRPV1, TRPV3 and TRPV4 of the TRPC and TRPV families, wh...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio821

    authors: Yoshida T,Inoue R,Morii T,Takahashi N,Yamamoto S,Hara Y,Tominaga M,Shimizu S,Sato Y,Mori Y

    更新日期:2006-11-01 00:00:00

  • Accessing chemical diversity from the uncultivated symbionts of small marine animals.

    abstract::Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV c...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2537

    authors: Smith TE,Pond CD,Pierce E,Harmer ZP,Kwan J,Zachariah MM,Harper MK,Wyche TP,Matainaho TK,Bugni TS,Barrows LR,Ireland CM,Schmidt EW

    更新日期:2018-02-01 00:00:00

  • Visualizing a protonated RNA state that modulates microRNA-21 maturation.

    abstract::MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-020-00667-5

    authors: Baisden JT,Boyer JA,Zhao B,Hammond SM,Zhang Q

    更新日期:2021-01-01 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

    doi:10.1038/s41589-020-0469-1

    authors: Gerry CJ,Schreiber SL

    更新日期:2020-04-01 00:00:00

  • Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth.

    abstract::The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1547

    authors: Duhr F,Déléris P,Raynaud F,Séveno M,Morisset-Lopez S,Mannoury la Cour C,Millan MJ,Bockaert J,Marin P,Chaumont-Dubel S

    更新日期:2014-07-01 00:00:00

  • A photochemical snapshot of CD22 binding.

    abstract::Identification of endogenous glycan-binding ligands for cell-surface receptors has been difficult. Incorporation of a photoactive sialic acid analog into B-cell surface glycoproteins suggests that CD22 molecules may cluster by binding carbohydrate antigens on neighboring CD22 molecules. ...

    journal_title:Nature chemical biology

    pub_type: 评论,新闻

    doi:10.1038/nchembio0705-69

    authors: Yarema KJ,Sun Z

    更新日期:2005-07-01 00:00:00

  • HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes.

    abstract::Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-020-0496-y

    authors: Xiao T,Frey G,Fu Q,Lavine CL,Scott DA,Seaman MS,Chou JJ,Chen B

    更新日期:2020-05-01 00:00:00

  • Molecular basis for ubiquitin ligase CRL2FEM1C-mediated recognition of C-degron.

    abstract::Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-020-00703-4

    authors: Yan X,Wang X,Li Y,Zhou M,Li Y,Song L,Mi W,Min J,Dong C

    更新日期:2021-01-04 00:00:00

  • Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation.

    abstract::Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2538

    authors: Olson CM,Jiang B,Erb MA,Liang Y,Doctor ZM,Zhang Z,Zhang T,Kwiatkowski N,Boukhali M,Green JL,Haas W,Nomanbhoy T,Fischer ES,Young RA,Bradner JE,Winter GE,Gray NS

    更新日期:2018-02-01 00:00:00

  • Transcriptional recorder.

    abstract:: ...

    journal_title:Nature chemical biology

    pub_type: 评论,杂志文章

    doi:10.1038/s41589-018-0174-5

    authors: Song Y

    更新日期:2018-12-01 00:00:00

  • A carbonate-forming Baeyer-Villiger monooxygenase.

    abstract::Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1527

    authors: Hu Y,Dietrich D,Xu W,Patel A,Thuss JA,Wang J,Yin WB,Qiao K,Houk KN,Vederas JC,Tang Y

    更新日期:2014-07-01 00:00:00

  • Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism.

    abstract::Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible g...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1136

    authors: Gut P,Baeza-Raja B,Andersson O,Hasenkamp L,Hsiao J,Hesselson D,Akassoglou K,Verdin E,Hirschey MD,Stainier DY

    更新日期:2013-02-01 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

    doi:10.1038/s41589-020-0506-0

    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

  • Allosteric inhibition of kinesin-5 modulates its processive directional motility.

    abstract::Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kin...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio812

    authors: Kwok BH,Kapitein LC,Kim JH,Peterman EJ,Schmidt CF,Kapoor TM

    更新日期:2006-09-01 00:00:00

  • Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs.

    abstract::Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-cou...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/s41589-019-0453-9

    authors: Bradley SJ,Molloy C,Valuskova P,Dwomoh L,Scarpa M,Rossi M,Finlayson L,Svensson KA,Chernet E,Barth VN,Gherbi K,Sykes DA,Wilson CA,Mistry R,Sexton PM,Christopoulos A,Mogg AJ,Rosethorne EM,Sakata S,John Challiss RA,B

    更新日期:2020-03-01 00:00:00

  • Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models.

    abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have distinct clinical features but a common pathology--cytoplasmic inclusions rich in transactive response element DNA-binding protein of 43 kDa (TDP43). Rare TDP43 mutations cause ALS or FTD, but abnormal TDP43 levels and localization may cause di...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1563

    authors: Barmada SJ,Serio A,Arjun A,Bilican B,Daub A,Ando DM,Tsvetkov A,Pleiss M,Li X,Peisach D,Shaw C,Chandran S,Finkbeiner S

    更新日期:2014-08-01 00:00:00

  • Interfacial enzyme kinetics of a membrane bound kinase analyzed by real-time MAS-NMR.

    abstract::The simultaneous observation of interdependent reactions within different phases as catalyzed by membrane-bound enzymes is still a challenging task. One such enzyme, the Escherichia coli integral membrane protein diacylglycerol kinase (DGK), is a key player in lipid regulation. It catalyzes the generation of phosphati...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.543

    authors: Ullrich SJ,Hellmich UA,Ullrich S,Glaubitz C

    更新日期:2011-05-01 00:00:00

  • Engineering peptide ligase specificity by proteomic identification of ligation sites.

    abstract::Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strat...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.2521

    authors: Weeks AM,Wells JA

    更新日期:2018-01-01 00:00:00

  • Electron handoff.

    abstract:: ...

    journal_title:Nature chemical biology

    pub_type: 评论,杂志文章

    doi:10.1038/s41589-018-0073-9

    authors: Deane C

    更新日期:2018-06-01 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

    doi:10.1038/nchembio.523

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

    更新日期:2011-03-01 00:00:00

  • Mechanism of hydrogen activation by [NiFe] hydrogenases.

    abstract::The active site of [NiFe] hydrogenases contains a strictly conserved arginine that suspends a guanidine nitrogen atom <4.5 Å above the nickel and iron atoms. The guanidine headgroup interacts with the side chains of two conserved aspartic acid residues to complete an outer-shell canopy that has thus far proved intract...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio.1976

    authors: Evans RM,Brooke EJ,Wehlin SA,Nomerotskaia E,Sargent F,Carr SB,Phillips SE,Armstrong FA

    更新日期:2016-01-01 00:00:00

  • Expanding chemical biology of 2-oxoglutarate oxygenases.

    abstract::Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...

    journal_title:Nature chemical biology

    pub_type: 杂志文章

    doi:10.1038/nchembio0308-152

    authors: Loenarz C,Schofield CJ

    更新日期:2008-03-01 00:00:00