Summary information and primary citation
- PDB-id
- 3trz; DSSR-derived features in text and JSON formats
- Class
- RNA binding protein-RNA
- Method
- X-ray (2.9 Å)
- Summary
- Mouse lin28a in complex with let-7d microrna pre-element
- Reference
- Nam Y, Chen C, Gregory RI, Chou JJ, Sliz P (2011): "Molecular Basis for Interaction of let-7 MicroRNAs with Lin28." Cell(Cambridge,Mass.), 147, 1080-1091. doi: 10.1016/j.cell.2011.10.020.
- 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.