Molecular basis for interaction of let-7 MicroRNAs with Lin28

Yunsun Nam, Casandra Chen, Richard I. Gregory, James J. Chou, Piotr Sliz

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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-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.

Original languageEnglish (US)
Pages (from-to)1080-1091
Number of pages12
JournalCell
Volume147
Issue number5
DOIs
Publication statusPublished - Nov 23 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nam, Y., Chen, C., Gregory, R. I., Chou, J. J., & Sliz, P. (2011). Molecular basis for interaction of let-7 MicroRNAs with Lin28. Cell, 147(5), 1080-1091. https://doi.org/10.1016/j.cell.2011.10.020