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Topics {✒️}

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WebPage:
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         headline:Ythdf2-mediated m6A mRNA clearance modulates neural development in mice
         description:N 6 -methyladenosine (m6A) modification in mRNAs was recently shown to be dynamically regulated, indicating a pivotal role in multiple developmental processes. Most recently, it was shown that the Mettl3-Mettl14 writer complex of this mark is required for the temporal control of cortical neurogenesis. The m6A reader protein Ythdf2 promotes mRNA degradation by recognizing m6A and recruiting the mRNA decay machinery. We show that the conditional depletion of the m6A reader protein Ythdf2 in mice causes lethality at late embryonic developmental stages, with embryos characterized by compromised neural development. We demonstrate that neural stem/progenitor cell (NSPC) self-renewal and spatiotemporal generation of neurons and other cell types are severely impacted by the loss of Ythdf2 in embryonic neocortex. Combining in vivo and in vitro assays, we show that the proliferation and differentiation capabilities of NSPCs decrease significantly in Ythdf2 −/− embryos. The Ythdf2 −/− neurons are unable to produce normally functioning neurites, leading to failure in recovery upon reactive oxygen species stimulation. Consistently, expression of genes enriched in neural development pathways is significantly disturbed. Detailed analysis of the m6A-methylomes of Ythdf2 −/− NSPCs identifies that the JAK-STAT cascade inhibitory genes contribute to neuroprotection and neurite outgrowths show increased expression and m6A enrichment. In agreement with the function of Ythdf2, delayed degradation of neuron differentiation-related m6A-containing mRNAs is seen in Ythdf2 −/− NSPCs. We show that the m6A reader protein Ythdf2 modulates neural development by promoting m6A-dependent degradation of neural development-related mRNA targets.
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             N -methyladenosine (m6A)
            Neural development
            Neurogenesis
            mRNA clearance
            Animal Genetics and Genomics
            Human Genetics
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Bioinformatics
            Evolutionary Biology
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      headline:Ythdf2-mediated m6A mRNA clearance modulates neural development in mice
      description:N 6 -methyladenosine (m6A) modification in mRNAs was recently shown to be dynamically regulated, indicating a pivotal role in multiple developmental processes. Most recently, it was shown that the Mettl3-Mettl14 writer complex of this mark is required for the temporal control of cortical neurogenesis. The m6A reader protein Ythdf2 promotes mRNA degradation by recognizing m6A and recruiting the mRNA decay machinery. We show that the conditional depletion of the m6A reader protein Ythdf2 in mice causes lethality at late embryonic developmental stages, with embryos characterized by compromised neural development. We demonstrate that neural stem/progenitor cell (NSPC) self-renewal and spatiotemporal generation of neurons and other cell types are severely impacted by the loss of Ythdf2 in embryonic neocortex. Combining in vivo and in vitro assays, we show that the proliferation and differentiation capabilities of NSPCs decrease significantly in Ythdf2 −/− embryos. The Ythdf2 −/− neurons are unable to produce normally functioning neurites, leading to failure in recovery upon reactive oxygen species stimulation. Consistently, expression of genes enriched in neural development pathways is significantly disturbed. Detailed analysis of the m6A-methylomes of Ythdf2 −/− NSPCs identifies that the JAK-STAT cascade inhibitory genes contribute to neuroprotection and neurite outgrowths show increased expression and m6A enrichment. In agreement with the function of Ythdf2, delayed degradation of neuron differentiation-related m6A-containing mRNAs is seen in Ythdf2 −/− NSPCs. We show that the m6A reader protein Ythdf2 modulates neural development by promoting m6A-dependent degradation of neural development-related mRNA targets.
      datePublished:2018-05-31T00:00:00Z
      dateModified:2018-05-31T00:00:00Z
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      keywords:
         Ythdf2
          N -methyladenosine (m6A)
         Neural development
         Neurogenesis
         mRNA clearance
         Animal Genetics and Genomics
         Human Genetics
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Bioinformatics
         Evolutionary Biology
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            name:Rajikala Suganthan
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            name:Chuan He
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            address:
               name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
      name:Magnar Bjørås
      affiliation:
            name:Oslo University Hospital
            address:
               name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
               type:PostalAddress
            type:Organization
            name:Norwegian University of Science and Technology (NTNU)
            address:
               name:Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Arne Klungland
      url:http://orcid.org/0000-0001-7274-3661
      affiliation:
            name:Oslo University Hospital
            address:
               name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
               type:PostalAddress
            type:Organization
            name:University of Oslo
            address:
               name:Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
      name:Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
      name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
      name:Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
      name:Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
      name:Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
      name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
      name:Department of Computational Biology, St. Jude Children’s Hospital, Memphis, USA
      name:Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
      name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
      name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
      name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
      name:Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, Chicago, USA
      name:Howard Hughes Medical Institute, The University of Chicago, Chicago, USA
      name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
      name:Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
      name:Department of Microbiology, Oslo University Hospital, Oslo, Norway
      name:Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

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