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Why double-stranded RNA resists condensation

The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to inter-DNA attraction and eventual condensation. Surprisingly, the condensation is suppressed in double-stranded RNA, which carries the same negative charge as DNA, but assumes a different double...

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Autores principales: Tolokh, Igor S., Pabit, Suzette A., Katz, Andrea M., Chen, Yujie, Drozdetski, Aleksander, Baker, Nathan, Pollack, Lois, Onufriev, Alexey V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176364/
https://www.ncbi.nlm.nih.gov/pubmed/25123663
http://dx.doi.org/10.1093/nar/gku756
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author Tolokh, Igor S.
Pabit, Suzette A.
Katz, Andrea M.
Chen, Yujie
Drozdetski, Aleksander
Baker, Nathan
Pollack, Lois
Onufriev, Alexey V.
author_facet Tolokh, Igor S.
Pabit, Suzette A.
Katz, Andrea M.
Chen, Yujie
Drozdetski, Aleksander
Baker, Nathan
Pollack, Lois
Onufriev, Alexey V.
author_sort Tolokh, Igor S.
collection PubMed
description The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to inter-DNA attraction and eventual condensation. Surprisingly, the condensation is suppressed in double-stranded RNA, which carries the same negative charge as DNA, but assumes a different double helical form. Here, we combine experiment and atomistic simulations to propose a mechanism that explains the variations in condensation of short (25 base-pairs) nucleic acid (NA) duplexes, from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA. Circular dichroism measurements suggest that duplex helical geometry is not the fundamental property that ultimately determines the observed differences in condensation. Instead, these differences are governed by the spatial variation of cobalt hexammine (CoHex) binding to NA. There are two major NA-CoHex binding modes—internal and external—distinguished by the proximity of bound CoHex to the helical axis. We find a significant difference, up to 5-fold, in the fraction of ions bound to the external surfaces of the different NA constructs studied. NA condensation propensity is determined by the fraction of CoHex ions in the external binding mode.
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spelling pubmed-41763642014-12-01 Why double-stranded RNA resists condensation Tolokh, Igor S. Pabit, Suzette A. Katz, Andrea M. Chen, Yujie Drozdetski, Aleksander Baker, Nathan Pollack, Lois Onufriev, Alexey V. Nucleic Acids Res Structural Biology The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to inter-DNA attraction and eventual condensation. Surprisingly, the condensation is suppressed in double-stranded RNA, which carries the same negative charge as DNA, but assumes a different double helical form. Here, we combine experiment and atomistic simulations to propose a mechanism that explains the variations in condensation of short (25 base-pairs) nucleic acid (NA) duplexes, from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA. Circular dichroism measurements suggest that duplex helical geometry is not the fundamental property that ultimately determines the observed differences in condensation. Instead, these differences are governed by the spatial variation of cobalt hexammine (CoHex) binding to NA. There are two major NA-CoHex binding modes—internal and external—distinguished by the proximity of bound CoHex to the helical axis. We find a significant difference, up to 5-fold, in the fraction of ions bound to the external surfaces of the different NA constructs studied. NA condensation propensity is determined by the fraction of CoHex ions in the external binding mode. Oxford University Press 2014-09-15 2014-08-14 /pmc/articles/PMC4176364/ /pubmed/25123663 http://dx.doi.org/10.1093/nar/gku756 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Tolokh, Igor S.
Pabit, Suzette A.
Katz, Andrea M.
Chen, Yujie
Drozdetski, Aleksander
Baker, Nathan
Pollack, Lois
Onufriev, Alexey V.
Why double-stranded RNA resists condensation
title Why double-stranded RNA resists condensation
title_full Why double-stranded RNA resists condensation
title_fullStr Why double-stranded RNA resists condensation
title_full_unstemmed Why double-stranded RNA resists condensation
title_short Why double-stranded RNA resists condensation
title_sort why double-stranded rna resists condensation
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176364/
https://www.ncbi.nlm.nih.gov/pubmed/25123663
http://dx.doi.org/10.1093/nar/gku756
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