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Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis

Let-7 is an important tumor-suppressive microRNA 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 contributin...

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Autores principales: Nicastro, Giuseppe, García-Mayoral, María Flor, Hollingworth, David, Kelly, Geoff, Martin, Stephen R., Briata, Paola, Gherzi, Roberto, Ramos, Andres
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605776/
https://www.ncbi.nlm.nih.gov/pubmed/23142982
http://dx.doi.org/10.1038/nsmb.2427
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author Nicastro, Giuseppe
García-Mayoral, María Flor
Hollingworth, David
Kelly, Geoff
Martin, Stephen R.
Briata, Paola
Gherzi, Roberto
Ramos, Andres
author_facet Nicastro, Giuseppe
García-Mayoral, María Flor
Hollingworth, David
Kelly, Geoff
Martin, Stephen R.
Briata, Paola
Gherzi, Roberto
Ramos, Andres
author_sort Nicastro, Giuseppe
collection PubMed
description Let-7 is an important tumor-suppressive microRNA 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 cell proliferation, apoptosis and differentiation. Here we analyze the molecular basis for KSRP-pre-Let-7 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 non-canonical 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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spelling pubmed-36057762013-06-01 Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis Nicastro, Giuseppe García-Mayoral, María Flor Hollingworth, David Kelly, Geoff Martin, Stephen R. Briata, Paola Gherzi, Roberto Ramos, Andres Nat Struct Mol Biol Article Let-7 is an important tumor-suppressive microRNA 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 cell proliferation, apoptosis and differentiation. Here we analyze the molecular basis for KSRP-pre-Let-7 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 non-canonical 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. 2012-11-11 2012-12 /pmc/articles/PMC3605776/ /pubmed/23142982 http://dx.doi.org/10.1038/nsmb.2427 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Nicastro, Giuseppe
García-Mayoral, María Flor
Hollingworth, David
Kelly, Geoff
Martin, Stephen R.
Briata, Paola
Gherzi, Roberto
Ramos, Andres
Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis
title Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis
title_full Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis
title_fullStr Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis
title_full_unstemmed Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis
title_short Non-canonical Guanine recognition mediates KSRP regulation of Let-7 biogenesis
title_sort non-canonical guanine recognition mediates ksrp regulation of let-7 biogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605776/
https://www.ncbi.nlm.nih.gov/pubmed/23142982
http://dx.doi.org/10.1038/nsmb.2427
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