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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{
  "DOI": "10.1016/j.molcel.2018.06.029", 
  "abstract": "<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>", 
  "author": [
    {
      "family": "Ustinanenko, Dmytro"
    }, 
    {
      "family": "Chiu, Hua-Sheng"
    }, 
    {
      "family": "Treiber, Thomas"
    }, 
    {
      "family": "Weyn-Vanhentenryck, Sebastien M"
    }, 
    {
      "family": "Treiber, Nora"
    }, 
    {
      "family": "Meister, Gunter"
    }, 
    {
      "family": "Sumazin, Pavel"
    }, 
    {
      "family": "Zhang, Chaolin"
    }
  ], 
  "id": "1445985", 
  "issued": {
    "date-parts": [
      [
        2018, 
        7, 
        18
      ]
    ]
  }, 
  "language": "eng", 
  "title": "LIN28 selectively modulates a subclass of let-7 microRNAs", 
  "type": "article-journal"
}
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