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pcdna5-frt-gfp-mcherry-3pgw backbone63 nature portfolio crispr/cas9 gene editing privacy policy fh-dhx36-e335a par-clip additional fh-dhx36-e335a par-clip experiment fh-dhx36 par-clip-derived rre par-clip-derived binding sites advertising hrp-conjugated goat anti-mouse nature communications hrp-conjugated goat anti-rabbit 5 µci µl−1 32p-γ-atp fh-dhx36-e335a par-clips fh-dhx36-e335a par-clip german research foundation intramural research program pfrt-flagha-dhx36-iso1-e335a pfrt-flagha-dhx36-iso2-e335a generated pfrt-flagha-dhx36-iso1 possibly allowing access plasmids pfrt-flagha-dhx36-iso2 dexd/h-box rna helicases dhx36-e335a par-clip targets heart development hek293 t-rex flp 4 mm l-arginine [u-13c6] 4 mm l-arginine [u-13c6 author information authors 75 µl ml−1 flag-m2 antibody fh-dhx36-e335a binding sites 8 mm l-lysine [u-13c6 rna-seq library preparation editing sequence-specific rna-binding proteins cytoplasm = anti-α-tubulin antibody tools reprints frac{{{\mathrm{count}}}}{{{\mathrm{total}} g-quadruplex structures contribute inducibly expressing fh-dhx36 nuclear = anti-histone 2b antibody par-clip binding sites dhx36-e335a par-clip research design transgenic wild-type helicase rna g-quadruplex structures helicase activity-dependent manner g-quadruplex dna accumulates fh-dhx36-e335a rnps separated

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         headline:DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions
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      headline:DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions
      description:Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress. Translation efficiency can be affected by mRNA stability and secondary RNA structures. Here the authors reveal that loss of DHX36 helicase activity leads to an accumulation of translationally inactive target mRNAs with G-rich structures in untranslated regions.
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      url:http://orcid.org/0000-0003-3080-6745
      affiliation:
            name:University of Würzburg
            address:
               name:Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany
               type:PostalAddress
            type:Organization
            name:University of Groningen
            address:
               name:European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
               type:PostalAddress
            type:Organization
            name:University Hospital Bonn
            address:
               name:Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany
      name:European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
      name:Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
      name:Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
      name:Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, USA
      name:Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
      name:European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
      name:Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
      name:Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, USA
      name:Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, USA
      name:Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, USA
      name:Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany
      name:European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
      name:Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany

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