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Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation

RNA transcripts that include expanded CCUG repeats are associated with myotonic dystrophy type 2. Crystal structures of two CCUG-containing oligomers show that the RNA strands associate into slipped duplexes that contain noncanonical C–U pairs that have apparently undergone tautomeric transition or...

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Autores principales: Rypniewski, Wojciech, Banaszak, Katarzyna, Kuliński, Tadeusz, Kiliszek, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691832/
https://www.ncbi.nlm.nih.gov/pubmed/26543073
http://dx.doi.org/10.1261/rna.052399.115
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author Rypniewski, Wojciech
Banaszak, Katarzyna
Kuliński, Tadeusz
Kiliszek, Agnieszka
author_facet Rypniewski, Wojciech
Banaszak, Katarzyna
Kuliński, Tadeusz
Kiliszek, Agnieszka
author_sort Rypniewski, Wojciech
collection PubMed
description RNA transcripts that include expanded CCUG repeats are associated with myotonic dystrophy type 2. Crystal structures of two CCUG-containing oligomers show that the RNA strands associate into slipped duplexes that contain noncanonical C–U pairs that have apparently undergone tautomeric transition or protonation resulting in an unusual Watson–Crick-like pairing. The overhanging ends of the duplexes interact forming U–U pairs, which also show tautomerism. Duplexes consisting of CCUG repeats are thermodynamically less stable than the trinucleotide repeats involved in the TRED genetic disorders, but introducing LNA residues increases their stability and raises the melting temperature of the studied oligomers by ∼10°C, allowing detailed crystallographic studies. Quantum mechanical calculations were performed to test the possibility of the tautomeric transitions or protonation within the noncanonical pairs. The results indicate that tautomeric or ionic shifts of nucleobases can manifest themselves in biological systems, supplementing the canonical “rules of engagement.”
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spelling pubmed-46918322017-01-01 Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation Rypniewski, Wojciech Banaszak, Katarzyna Kuliński, Tadeusz Kiliszek, Agnieszka RNA Article RNA transcripts that include expanded CCUG repeats are associated with myotonic dystrophy type 2. Crystal structures of two CCUG-containing oligomers show that the RNA strands associate into slipped duplexes that contain noncanonical C–U pairs that have apparently undergone tautomeric transition or protonation resulting in an unusual Watson–Crick-like pairing. The overhanging ends of the duplexes interact forming U–U pairs, which also show tautomerism. Duplexes consisting of CCUG repeats are thermodynamically less stable than the trinucleotide repeats involved in the TRED genetic disorders, but introducing LNA residues increases their stability and raises the melting temperature of the studied oligomers by ∼10°C, allowing detailed crystallographic studies. Quantum mechanical calculations were performed to test the possibility of the tautomeric transitions or protonation within the noncanonical pairs. The results indicate that tautomeric or ionic shifts of nucleobases can manifest themselves in biological systems, supplementing the canonical “rules of engagement.” Cold Spring Harbor Laboratory Press 2016-01 /pmc/articles/PMC4691832/ /pubmed/26543073 http://dx.doi.org/10.1261/rna.052399.115 Text en © 2015 Rypniewski et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Rypniewski, Wojciech
Banaszak, Katarzyna
Kuliński, Tadeusz
Kiliszek, Agnieszka
Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation
title Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation
title_full Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation
title_fullStr Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation
title_full_unstemmed Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation
title_short Watson–Crick-like pairs in CCUG repeats: evidence for tautomeric shifts or protonation
title_sort watson–crick-like pairs in ccug repeats: evidence for tautomeric shifts or protonation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691832/
https://www.ncbi.nlm.nih.gov/pubmed/26543073
http://dx.doi.org/10.1261/rna.052399.115
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