1445985
doi
10.1016/j.molcel.2018.06.029
oai:zenodo.org:1445985
user-precise
user-eu
Chiu, Hua-Sheng
Texas Children's Cancer Center, Department of Pediatrics, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
Treiber, Thomas
Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany
Weyn-Vanhentenryck, Sebastien M
Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA
Treiber, Nora
Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany
Meister, Gunter
Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany
Sumazin, Pavel
Texas Children's Cancer Center, Department of Pediatrics, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
Zhang, Chaolin
Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA
LIN28 selectively modulates a subclass of let-7 microRNAs
Ustinanenko, Dmytro
Department of Systems Biology, Department of Biochemistry and Molecular Biophysics, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
LIN28
let-7 microRNA biogenesis
cold shock domani
bipartite binding
selective suppression
<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) —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 3สน 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.</p>
Zenodo
2018-07-18
info:eu-repo/semantics/article
1445984
user-precise
user-eu
award_title=PERSONALIZED ENGINE FOR CANCER INTEGRATIVE STUDY AND EVALUATION; award_number=668858; award_identifiers_scheme=url; award_identifiers_identifier=https://cordis.europa.eu/projects/668858; funder_id=00k4n6c32; funder_name=European Commission;
1579541605.180293
752513
md5:64e900f11624dd5cabb53ef7a3de692f
https://zenodo.org/records/1445985/files/Lin28-selectively-modulates.pdf
public