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Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Steffen Fabio D., Khier Mokrane, Kowerko Danny, Cunha Richard A., Börner Richard, Sigel Roland K. O.,
Project Metal Ions in Structure and Function of Regulatory RNAs
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Original article (peer-reviewed)

Journal Nature Communications
Volume (Issue) 11(1)
Page(s) 104 - 104
Title of proceedings Nature Communications
DOI 10.1038/s41467-019-13683-4

Open Access

Type of Open Access Publisher (Gold Open Access)


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.