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Cell. 2011 Nov 23;147(5):1080-91. doi: 10.1016/j.cell.2011.10.020. Epub 2011 Nov 10.

Molecular basis for interaction of let-7 microRNAs with Lin28.

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  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
22078496
[PubMed - indexed for MEDLINE]
PMCID:
PMC3277843
Free PMC Article
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