Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-12

AUTHORS

Giuseppe Nicastro, María Flor García-Mayoral, David Hollingworth, Geoff Kelly, Stephen R Martin, Paola Briata, Roberto Gherzi, Andres Ramos

ABSTRACT

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. More... »

PAGES

1282

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nsmb.2427

DOI

http://dx.doi.org/10.1038/nsmb.2427

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018615224

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23142982


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