Structural insights of the pre-let-7 interaction with LIN28B.

The Let-7:LIN28 regulatory loop is a paradigm in miRNA regulation. LIN28 harbors two RNA binding domains, which interact with well-conserved sequences in pre-let-7 RNAs, the GNGAY and the GGAG motifs. Here, the differential binding between LIN28B and pre-let-7 members was associated with the structural characteristics of the pre-let-7 family mapped by SHAPE, uncovering diverse structural patterns within pre-let-7 members. Pre-let-7 mutants supported a relevant role of the GGAG motif location and the preE-stem stability for the interaction with LIN28B. Based on these results, we propose a core RNA structure for LIN28B interaction.