Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 13, Pages 6528-6543Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky490
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Funding
- Czech Science Foundation [P305/12/G034]
- Ministry of Education, Youth and Sports of the Czech Republic [LO1305]
- Praemium Academiae
- SYMBIT by ERDF [CZ.02.1.01/0.0/0.0/15_003/0000477]
- National Grid Infrastructure MetaCentrum [LM2010005]
- state of Hesse
- Molecular mechanisms of RNA-based regulation [CRC 902]
- Institute of Biophysics of the Czech Academy of Sciences
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The neomycin sensing riboswitch is the smallest biologically functional RNA riboswitch, forming a hairpin capped with a U-turn loop-a well-known RNA motif containing a conserved uracil. It was shown previously that a U -> C substitution of the eponymous conserved uracil does not alter the riboswitch structure due to C protonation at N3. Furthermore, cytosine is evolutionary permitted to replace uracil in other U-turns. Here, we use molecular dynamics simulations to study the molecular basis of this substitution in the neomycin sensing riboswitch and show that a structure-stabilizing monovalent cation-binding site in the wild-type RNA is the main reason for its negligible structural effect. We then use NMR spectroscopy to confirm the existence of this cation-binding site and to demonstrate its effects on RNA stability. Lastly, using quantum chemical calculations, we show that the cation-binding site is altering the electronic environment of the wild-type U-turn so that it is more similar to the cytosine mutant. The study reveals an amazingly complex and delicate interplay between various energy contributions shaping up the 3D structure and evolution of nucleic acids.
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