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Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts
The fidelity of group II intron self-splicing and retrohoming relies on long-range tertiary interactions between the intron and its flanking exons. By single-molecule FRET, we explore the binding kinetics of the most important, structurally conserved contact, the exon and intron binding site 1 (EBS1...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949254/ https://www.ncbi.nlm.nih.gov/pubmed/31913262 http://dx.doi.org/10.1038/s41467-019-13683-4 |
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author | Steffen, Fabio D. Khier, Mokrane Kowerko, Danny Cunha, Richard A. Börner, Richard Sigel, Roland K. O. |
author_facet | Steffen, Fabio D. Khier, Mokrane Kowerko, Danny Cunha, Richard A. Börner, Richard Sigel, Roland K. O. |
author_sort | Steffen, Fabio D. |
collection | PubMed |
description | The fidelity of group II intron self-splicing and retrohoming relies on long-range tertiary interactions between the intron and its flanking exons. By single-molecule FRET, we explore the binding kinetics of the most important, structurally conserved contact, the exon and intron binding site 1 (EBS1/IBS1). A comparison of RNA-RNA and RNA-DNA hybrid contacts identifies transient metal ion binding as a major source of kinetic heterogeneity which typically appears in the form of degenerate FRET states. Molecular dynamics simulations suggest a structural link between heterogeneity and the sugar conformation at the exon-intron binding interface. While Mg(2+) ions lock the exon in place and give rise to long dwell times in the exon bound FRET state, sugar puckering alleviates this structural rigidity and likely promotes exon release. The interplay of sugar puckering and metal ion coordination may be an important mechanism to balance binding affinities of RNA and DNA interactions in general. |
format | Online Article Text |
id | pubmed-6949254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69492542020-01-10 Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts Steffen, Fabio D. Khier, Mokrane Kowerko, Danny Cunha, Richard A. Börner, Richard Sigel, Roland K. O. Nat Commun Article The fidelity of group II intron self-splicing and retrohoming relies on long-range tertiary interactions between the intron and its flanking exons. By single-molecule FRET, we explore the binding kinetics of the most important, structurally conserved contact, the exon and intron binding site 1 (EBS1/IBS1). A comparison of RNA-RNA and RNA-DNA hybrid contacts identifies transient metal ion binding as a major source of kinetic heterogeneity which typically appears in the form of degenerate FRET states. Molecular dynamics simulations suggest a structural link between heterogeneity and the sugar conformation at the exon-intron binding interface. While Mg(2+) ions lock the exon in place and give rise to long dwell times in the exon bound FRET state, sugar puckering alleviates this structural rigidity and likely promotes exon release. The interplay of sugar puckering and metal ion coordination may be an important mechanism to balance binding affinities of RNA and DNA interactions in general. Nature Publishing Group UK 2020-01-08 /pmc/articles/PMC6949254/ /pubmed/31913262 http://dx.doi.org/10.1038/s41467-019-13683-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Steffen, Fabio D. Khier, Mokrane Kowerko, Danny Cunha, Richard A. Börner, Richard Sigel, Roland K. O. Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts |
title | Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts |
title_full | Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts |
title_fullStr | Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts |
title_full_unstemmed | Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts |
title_short | Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts |
title_sort | metal ions and sugar puckering balance single-molecule kinetic heterogeneity in rna and dna tertiary contacts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949254/ https://www.ncbi.nlm.nih.gov/pubmed/31913262 http://dx.doi.org/10.1038/s41467-019-13683-4 |
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