RT Journal Article
SR Electronic
T1 LIN28 selectively modulates a subclass of let-7 microRNAs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 202036
DO 10.1101/202036
A1 Dmytro Ustianenko
A1 Hua-Sheng Chiu
A1 Sebastien M. Weyn-Vanhentenryck
A1 Pavel Sumazin
A1 Chaolin Zhang
YR 2017
UL http://biorxiv.org/content/early/2017/10/12/202036.abstract
AB LIN28 is a bipartite RNA-binding protein that post-transcriptionally inhibits 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 family into Class I precursors with both CSD and ZKD binding sites and Class II precursors with ZKD but no CSD binding sites. LIN28 in vivo recognition—and subsequent 3′ uridylation and degradation—of Class I 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 with potential implication in development and cancer.