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Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis

Nicastro, G; García-Mayoral, MF; Hollingworth, D; Kelly, G; Martin, SR; Briata, P; Gherzi, R; (2012) Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis. Nature Structural & Molecular Biology , 19 (12) pp. 1282-1286. 10.1038/nsmb.2427. Green open access

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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.

Type: Article
Title: Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nsmb.2427
Publisher version: http://dx.doi.org/10.1038/nsmb.2427
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Humans, MicroRNAs, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, RNA-Binding Proteins, Trans-Activators
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1403853
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