[HTML][HTML] Molecular basis for interaction of let-7 microRNAs with Lin28

Y Nam, C Chen, RI Gregory, JJ Chou, P Sliz - Cell, 2011 - cell.com
Y Nam, C Chen, RI Gregory, JJ Chou, P Sliz
Cell, 2011cell.com
MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression.
Among these, members of the let-7 miRNA family control many cell-fate determination genes
to influence pluripotency, differentiation, and transformation. Lin28 is a specific,
posttranscriptional inhibitor of let-7 biogenesis. We report crystal structures of mouse Lin28
in complex with sequences from let-7d, let-7-f1, and let-7g precursors. The two folded
domains of Lin28 recognize two distinct regions of the RNA and are sufficient for inhibition of …
Summary
MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression. Among these, members of the let-7 miRNA family control many cell-fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, posttranscriptional inhibitor of let-7 biogenesis. We report crystal structures of mouse Lin28 in complex with sequences from let-7d, let-7-f1, and let-7g precursors. The two folded domains of Lin28 recognize two distinct regions of the RNA and are sufficient for inhibition of let-7 in vivo. We also show by NMR spectroscopy that the linker connecting the two folded domains is flexible, accommodating Lin28 binding to diverse let-7 family members. Protein-RNA complex formation imposes specific conformations on both components that could affect downstream recognition by other processing factors. Our data provide a molecular explanation for Lin28 specificity and a model for how it regulates let-7.
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