Journal article Open Access

LIN28 selectively modulates a subclass of let-7 microRNAs

Ustinanenko, Dmytro; Chiu, Hua-Sheng; Treiber, Thomas; Weyn-Vanhentenryck, Sebastien M; Treiber, Nora; Meister, Gunter; Sumazin, Pavel; Zhang, Chaolin


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      {
        "affiliation": "Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA", 
        "name": "Ustinanenko, Dmytro"
      }, 
      {
        "affiliation": "Texas Children's Cancer Center, Department of Pediatrics, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA", 
        "name": "Chiu, Hua-Sheng"
      }, 
      {
        "affiliation": "Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany", 
        "name": "Treiber, Thomas"
      }, 
      {
        "affiliation": "Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA", 
        "name": "Weyn-Vanhentenryck, Sebastien M"
      }, 
      {
        "affiliation": "Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany", 
        "name": "Treiber, Nora"
      }, 
      {
        "affiliation": "Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany", 
        "name": "Meister, Gunter"
      }, 
      {
        "affiliation": "Texas Children's Cancer Center, Department of Pediatrics, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA", 
        "name": "Sumazin, Pavel"
      }, 
      {
        "affiliation": "Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA", 
        "name": "Zhang, Chaolin"
      }
    ], 
    "description": "<p>LIN28 is a bipartite RNA-binding protein that post-transcriptionally inhibits the biogenesis of let-7 microRNAs to regulate development and influence disease states. However, the mechanisms of let-7 suppression remains poorly understood, because LIN28 recognition depends on coordinated targeting by both the zinc knuckle domain (ZKD) &mdash;which binds a GGAG-like element in the precursor&mdash;and the cold shock domain (CSD), whose binding sites have not been systematically characterized. By leveraging single-nucleotide-resolution mapping of LIN28 binding sites in vivo, we determined that the CSD recognizes a (U)GAU motif. This motif partitions the let-7 microRNAs into two subclasses, precursors with both CSD and ZKD binding sites (CSD+) and precursors with ZKD but no CSD binding sites (CSD-). LIN28 in vivo recognition&mdash;and subsequent 3\u02b9 uridylation and degradation&mdash;of CSD+ precursors is more efficient, leading to their stronger suppression in LIN28-activated cells and cancers. Thus, CSD binding sites amplify the effects of the LIN28 activation.</p>", 
    "doi": "10.1016/j.molcel.2018.06.029", 
    "grants": [
      {
        "acronym": "PrECISE", 
        "code": "668858", 
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            "EC"
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          "name": "European Commission"
        }, 
        "links": {
          "self": "https://zenodo.org/api/grants/10.13039/501100000780::668858"
        }, 
        "program": "H2020", 
        "title": "PERSONALIZED ENGINE FOR CANCER INTEGRATIVE STUDY AND EVALUATION"
      }
    ], 
    "keywords": [
      "LIN28", 
      "let-7 microRNA biogenesis", 
      "cold shock domani", 
      "bipartite binding", 
      "selective suppression"
    ], 
    "language": "eng", 
    "license": {
      "id": "CC-BY-4.0"
    }, 
    "publication_date": "2018-07-18", 
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    "title": "LIN28 selectively modulates a subclass of let-7 microRNAs"
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    34393
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