期刊
MOLECULAR CELL
卷 71, 期 2, 页码 271-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2018.06.029
关键词
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资金
- National Institutes of Health (NIH) [R01NS089676, R01GM124486, R21NS098172, R03HG009528, S10OD012351, S10OD021764]
- Simons Foundation Autism Research Initiative [307711]
- European Union's Horizon 2020 Research and Innovation Programme [668858]
- European Research Council (ERC) [682291]
- European Research Council (ERC) [682291] Funding Source: European Research Council (ERC)
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.
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