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ythdf, rna, deadenylation, article, fig, mrna, google, scholar, cnot, cas, rnas, cells, complex, cell, ccrnot, decay, domain, macontaining, pubmed, reporter, central, nature, modification, proteins, caf, endogenous, interaction, fragments, bgplac, bgboxb, binding, region, protein, supplementary, deadenylase, degradation, polya, assay, assays, shanghai, human, bgplacmut, plasmids, mrnas, antibody, ythdfc, direct, recruitment, zhao, accelerated,

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nature portfolio privacy policy plasmids encoding λn-flag-ythdf2/ythdf1/ythdf3/ythdf2 superdex-g200 size-exclusion column advertising planned parenthood research photo-crosslinking-assisted m6a sequencing constitutively transcribed α-globin-gapdh social media reversible nature methods plasmid constructions open reading frame 0/ reprints additional information transcriptional pulse-chase assay development bg-plac2-mut undergoing deadenylation high-resolution n6-methyladenosine n6-methyladenosine-dependent regulation λn-flag-ythdf2 tethering system anti-flag m2 antibody /n-rich n-terminal region real-time quantitative pcr research nature 502 nature 403 nature 485 nature 505 nature 518 nature 409 nature 429 nature anti-flag affinity gel rna n6-methyladenosine methyltransferase open biosystems n6-methyladenosine modification involved hela-tta cell line quantitative reverse transcriptase–pcr hela-tta cells growing transiently inducible β-globin 5′-phosphate-dependent exonuclease xrn-1 rna-sequencing data obtained references jones high-resolution mapping reveals flag-tagged ythdf2 due anti-ha-hrp antibodies pa-m6a-seq relative cis-acting regulatory sequences 1 ml tris-buffered saline thermo fisher scientific

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         headline:YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex
         description:Methylation at the N6 position of adenosine (m6A) is the most abundant RNA modification within protein-coding and long noncoding RNAs in eukaryotes and is a reversible process with important biological functions. YT521-B homology domain family (YTHDF) proteins are the readers of m6A, the binding of which results in the alteration of the translation efficiency and stability of m6A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m6A-containing RNAs is poorly understood. Here we report that m6A-containing RNAs exhibit accelerated deadenylation that is mediated by the CCR4–NOT deadenylase complex. We further show that YTHDF2 recruits the CCR4–NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and that this recruitment is essential for the deadenylation of m6A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m6A-containing RNAs in mammalian cells. The YTHDF family of proteins are able to bind and regulate the stability of methylated N6 RNA. Here the authors show that this decreased m6A RNA stability is mediated by direct recruitment of the CCR4–NOT deadenylase complex through YTHDF proteins.
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      headline:YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex
      description:Methylation at the N6 position of adenosine (m6A) is the most abundant RNA modification within protein-coding and long noncoding RNAs in eukaryotes and is a reversible process with important biological functions. YT521-B homology domain family (YTHDF) proteins are the readers of m6A, the binding of which results in the alteration of the translation efficiency and stability of m6A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m6A-containing RNAs is poorly understood. Here we report that m6A-containing RNAs exhibit accelerated deadenylation that is mediated by the CCR4–NOT deadenylase complex. We further show that YTHDF2 recruits the CCR4–NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and that this recruitment is essential for the deadenylation of m6A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m6A-containing RNAs in mammalian cells. The YTHDF family of proteins are able to bind and regulate the stability of methylated N6 RNA. Here the authors show that this decreased m6A RNA stability is mediated by direct recruitment of the CCR4–NOT deadenylase complex through YTHDF proteins.
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      address:
         name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
         type:PostalAddress
      name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
      address:
         name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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      name:Hao Du
      affiliation:
            name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
            address:
               name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
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            name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences
            address:
               name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
            address:
               name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Ya Zhao
      affiliation:
            name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
            address:
               name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences
            address:
               name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
            address:
               name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Jinqiu He
      affiliation:
            name:State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University
            address:
               name:Department of Biochemistry, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Yao Zhang
      affiliation:
            name:Shanghai Institute of Planned Parenthood Research
            address:
               name:Shanghai Institute of Planned Parenthood Research, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Hairui Xi
      affiliation:
            name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
            address:
               name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences
            address:
               name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
            address:
               name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:School of Life Sciences, Shanghai University
            address:
               name:School of Life Sciences, Shanghai University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Mofang Liu
      affiliation:
            name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
            address:
               name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Jinbiao Ma
      affiliation:
            name:State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University
            address:
               name:Department of Biochemistry, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Ligang Wu
      affiliation:
            name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
            address:
               name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences
            address:
               name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
            address:
               name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
      name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
      name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
      name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
      name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
      name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
      name:Department of Biochemistry, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China
      name:Shanghai Institute of Planned Parenthood Research, Shanghai, China
      name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
      name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
      name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
      name:School of Life Sciences, Shanghai University, Shanghai, China
      name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
      name:Department of Biochemistry, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China
      name:State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
      name:CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai, China
      name:Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

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