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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 (2020). Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts. Nature Communications, 11(1):104.

Abstract

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 Mg2+ 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.

Abstract

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 Mg2+ 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > General Chemistry
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Physical Sciences > General Physics and Astronomy
Uncontrolled Keywords:General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry
Language:English
Date:1 December 2020
Deposited On:21 Feb 2020 07:14
Last Modified:27 Nov 2020 07:33
Publisher:Nature Publishing Group
ISSN:2041-1723
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41467-019-13683-4
Project Information:
  • : FunderFP7
  • : Grant ID259092
  • : Project TitleMetal Ions and Metal Ion Complexes Guiding Folding and Function of Single RNA Molecules
  • : FunderUZH
  • : Grant IDFK-17-098
  • : Project TitleForschungskredit
  • : FunderUZH
  • : Grant IDFK-14-096/15-96
  • : Project TitleForschugskredit

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