Journal
RNA
Volume 22, Issue 1, Pages 22-31Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.052399.115
Keywords
CCUG repeats; myotonic dystrophy type 2; X-ray crystallography; thermodynamics; tautomerism
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Funding
- National Science Centre (Poland) [UMO-2011/01/B/NZ1/04429]
- Ministry of Science and Higher Education (Poland) [NN519405037, 01/KNOW2/2014]
- European Commission (the Seventh Framework Programme)
- BioStruct-X project [283570]
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RNA transcripts that include expanded CCUG repeats are associated with myotonic dystrophy type 2. Crystal structures of two CCUG-containing oligomers show that the RNA strands associate into slipped duplexes that contain noncanonical C-U pairs that have apparently undergone tautomeric transition or protonation resulting in an unusual Watson Crick-like pairing. The overhanging ends of the duplexes interact forming U-U pairs, which also show tautomerism. Duplexes consisting of CCUG repeats are thermodynamically less stable than the trinucleotide repeats involved in the TRED genetic disorders, but introducing LNA residues increases their stability and raises the melting temperature of the studied oligomers by similar to 10 degrees C, allowing detailed crystallographic studies. Quantum mechanical calculations were performed to test the possibility of the tautomeric transitions or protonation within the noncanonical pairs. The results indicate that tautomeric or ionic shifts of nucleobases can manifest themselves in biological systems, supplementing the canonical rules of engagement.
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