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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<oai_dc:dc xmlns:dc="" xmlns:oai_dc="" xmlns:xsi="" xsi:schemaLocation="">
  <dc:creator>Ustinanenko, Dmytro</dc:creator>
  <dc:creator>Chiu, Hua-Sheng</dc:creator>
  <dc:creator>Treiber, Thomas</dc:creator>
  <dc:creator>Weyn-Vanhentenryck, Sebastien M</dc:creator>
  <dc:creator>Treiber, Nora</dc:creator>
  <dc:creator>Meister, Gunter</dc:creator>
  <dc:creator>Sumazin, Pavel</dc:creator>
  <dc:creator>Zhang, Chaolin</dc:creator>
  <dc:description>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) —which binds a GGAG-like element in the precursor—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—and subsequent 3ʹ uridylation and degradation—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.</dc:description>
  <dc:subject>let-7 microRNA biogenesis</dc:subject>
  <dc:subject>cold shock domani</dc:subject>
  <dc:subject>bipartite binding</dc:subject>
  <dc:subject>selective suppression</dc:subject>
  <dc:title>LIN28 selectively modulates a subclass of let-7 microRNAs</dc:title>
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