3TS2: Mouse Lin28a In Complex With Let-7g Microrna Pre-Element

Citation:
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.
PDB ID: 3TS2Download
MMDB ID: 95086
PDB Deposition Date: 2011/9/11
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 2.01  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3TS2: tetrameric; determined by author and by software (PISA)
Molecular Components in 3TS2
Label Count Molecule
Proteins (2 molecules)
2
Protein Lin-28 Homolog a(Gene symbol: Lin28a)
Molecule annotation
Nucleotide(1 molecule)
2
RNA (5'- R(*gp*gp*gp*gp*up*cp*up*ap*up*gp*ap*up*ap*cp*cp*ap*cp*cp*cp*cp*gp*gp* Ap*g)-3')
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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