Molecular basis for interaction of let-7 microRNAs with Lin28.
Publication Type:Journal Article
Source:Cell, Volume 147, Issue 5, p.1080-91 (2011)
Keywords:Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Crystallography, X-Ray, Mice, MicroRNAs, Models, Molecular, Molecular Sequence Data, RNA-Binding Proteins, Sequence Alignment
<p>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-7 g 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.</p>