Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine.
Loading...
Embargo End Date
ICR Authors
Authors
Mieczkowski, M
Steinmetzger, C
Bessi, I
Lenz, A-K
Schmiedel, A
Holzapfel, M
Lambert, C
Pena, V
Höbartner, C
Steinmetzger, C
Bessi, I
Lenz, A-K
Schmiedel, A
Holzapfel, M
Lambert, C
Pena, V
Höbartner, C
Document Type
Journal Article
Date
2021-06-10
Date Accepted
2021-05-25
Abstract
Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural and mechanistic basis of fluorescence activation by crystallography and time-resolved optical spectroscopy. Two co-crystal structures of the Chili RNA with positively charged DMHBO+ and DMHBI+ ligands revealed a G-quadruplex and a trans-sugar-sugar edge G:G base pair that immobilize the ligand by π-π stacking. A Watson-Crick G:C base pair in the fluorophore binding site establishes a short hydrogen bond between the N7 of guanine and the phenolic OH of the ligand. Ultrafast excited state proton transfer (ESPT) from the neutral chromophore to the RNA was found with a time constant of 130 fs and revealed the mode of action of the large Stokes shift fluorogenic RNA aptamer.
Citation
Nature communications, 2021, 12 (1), pp. 3549 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Mechanisms and regulation of pre-mRNA splicing
Mechanisms and regulation of pre-mRNA splicing
Mechanisms and regulation of pre-mRNA splicing