| Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis. | |
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MedLine Citation:
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PMID: 23142982 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Let-7 is an important tumor-suppressive microRNA (miRNA) that acts as an on-off switch for cellular differentiation and regulates the expression of a set of human oncogenes. Binding of the human KSRP protein to let-7 miRNA precursors positively regulates their processing to mature let-7, thereby contributing to control of cell proliferation, apoptosis and differentiation. Here we analyze the molecular basis for KSRP-let-7 precursor selectivity and show how the third KH domain of the protein recognizes a G-rich sequence in the pre-let-7 terminal loop and dominates the interaction. The structure of the KH3-RNA complex explains the protein recognition of this noncanonical KH target sequence, and we demonstrate that the specificity of this binding is crucial for the functional interaction between the protein and the miRNA precursor. |
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Authors:
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Giuseppe Nicastro; María Flor García-Mayoral; David Hollingworth; Geoff Kelly; Stephen R Martin; Paola Briata; Roberto Gherzi; Andres Ramos |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-11-11 |
Journal Detail:
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Title: Nature structural & molecular biology Volume: 19 ISSN: 1545-9985 ISO Abbreviation: Nat. Struct. Mol. Biol. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-05 Completed Date: 2013-02-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101186374 Medline TA: Nat Struct Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1282-6 Citation Subset: IM |
Affiliation:
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Molecular Structure Division, Medical Research Council National Institute for Medical Research, London, UK. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/4B8T |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Humans MicroRNAs / biosynthesis* Models, Molecular Nuclear Magnetic Resonance, Biomolecular RNA-Binding Proteins / physiology* Trans-Activators / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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U117533887//Medical Research Council; U117570592//Medical Research Council; U117574558//Medical Research Council; WT082088MA//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/KHSRP protein, human; 0/MicroRNAs; 0/RNA-Binding Proteins; 0/Trans-Activators; 0/mirnlet7 microRNA, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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