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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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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. |
format | Online Article Text |
id | pubmed-3605776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
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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