Ustianenko, Dmytro and Chiu, Hua-Sheng and Treiber, Thomas and Weyn-Vanhentenryck, Sebastien M. and Treiber, Nora and Meister, Gunter and Sumazin, Pavel and Zhang, Chaolin (2018) LIN28 Selectively Modulates a Subclass of Let-7 MicroRNAs. MOLECULAR CELL, 71 (2). 271-+. ISSN 1097-2765, 1097-4164
Full text not available from this repository. (Request a copy)Abstract
LIN28 is a bipartite RNA-binding protein that posttranscriptionallyinhibits the biogenesis of let-7 microRNAs to regulate development and influence disease states. However, the mechanisms of let-7 suppression remain 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 3' 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 regulatory effects of LIN28.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RNA-BINDING PROTEINS; MESSENGER-RNAS; NUCLEAR EXPORT; HITS-CLIP; PATHWAY; SITES; TRANSCRIPTION; INTERFERENCE; BIOGENESIS; MECHANISMS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Mar 2020 12:59 |
| Last Modified: | 06 Mar 2020 12:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14223 |
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