Molecular basis for interaction of let-7 MicroRNAs with Lin28

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

Research output: Contribution to journalArticle

207 Citations (Scopus)

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
StatePublished - Nov 23 2011

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MicroRNAs
RNA
Small Untranslated RNA
Gene expression
Nuclear magnetic resonance spectroscopy
Conformations
Magnetic Resonance Spectroscopy
Genes
Crystal structure
Gene Expression
Molecules
Processing
Proteins
Recognition (Psychology)
Inhibition (Psychology)

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

Molecular basis for interaction of let-7 MicroRNAs with Lin28. / Nam, Yunsun; Chen, Casandra; Gregory, Richard I.; Chou, James J.; Sliz, Piotr.

In: Cell, Vol. 147, No. 5, 23.11.2011, p. 1080-1091.

Research output: Contribution to journalArticle

Nam, Y, Chen, C, Gregory, RI, Chou, JJ & Sliz, P 2011, 'Molecular basis for interaction of let-7 MicroRNAs with Lin28', Cell, vol. 147, no. 5, pp. 1080-1091. https://doi.org/10.1016/j.cell.2011.10.020
Nam, Yunsun ; Chen, Casandra ; Gregory, Richard I. ; Chou, James J. ; Sliz, Piotr. / Molecular basis for interaction of let-7 MicroRNAs with Lin28. In: Cell. 2011 ; Vol. 147, No. 5. pp. 1080-1091.
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