Document Detail


Molecular basis for interaction of let-7 microRNAs with Lin28.
MedLine Citation:
PMID:  22078496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yunsun Nam; Casandra Chen; Richard I Gregory; James J Chou; Piotr Sliz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-10
Journal Detail:
Title:  Cell     Volume:  147     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-28     Completed Date:  2012-01-23     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1080-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
PDB/3TRZ;  3TS0;  3TS2
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Crystallography, X-Ray
Mice
MicroRNAs / chemistry*,  metabolism
Models, Molecular
Molecular Sequence Data
RNA-Binding Proteins / chemistry*,  metabolism
Sequence Alignment
Grant Support
ID/Acronym/Agency:
5U54GM094608/GM/NIGMS NIH HHS; U54 GM094608/GM/NIGMS NIH HHS; U54 GM094608-01/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Lin-28 protein, mouse; 0/MicroRNAs; 0/RNA-Binding Proteins; 0/mirnlet7 microRNA, mouse
Comments/Corrections

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