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Biochemistry. 2018 Apr 10;57(14):2121-2131. doi: 10.1021/acs.biochem.7b01306. Epub 2018 Mar 23.

Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops.

Author information

1
Department of Biochemistry and Biophysics , University of Rochester School of Medicine and Dentistry , Rochester , New York 14642 , United States.
2
Center for RNA Biology , University of Rochester School of Medicine and Dentistry , Rochester , New York 14642 , United States.
3
Department of Chemistry , University of Oklahoma , Norman , Oklahoma 73019 , United States.
4
Department of Chemistry , Saint Louis University , St. Louis , Missouri 63103 , United States.
5
Department of Chemistry , University of Rochester , Rochester , New York 14627 , United States.

Abstract

GU base pairs are important RNA structural motifs and often close loops. Accurate prediction of RNA structures relies upon understanding the interactions determining structure. The thermodynamics of some 2 × 2 nucleotide internal loops closed by GU pairs are not well understood. Here, several self-complementary oligonucleotide sequences expected to form duplexes with 2 × 2 nucleotide internal loops closed by GU pairs were investigated. Surprisingly, nuclear magnetic resonance revealed that many of the sequences exist in equilibrium between hairpin and duplex conformations. This equilibrium is not observed with loops closed by Watson-Crick pairs. To measure the thermodynamics of some 2 × 2 nucleotide internal loops closed by GU pairs, non-self-complementary sequences that preclude formation of hairpins were designed. The measured thermodynamics indicate that some internal loops closed by GU pairs are unusually unstable. This instability accounts for the observed equilibria between duplex and hairpin conformations. Moreover, it suggests that future three-dimensional structures of loops closed by GU pairs may reveal interactions that unexpectedly destabilize folding.

PMID:
29570276
PMCID:
PMC5963885
DOI:
10.1021/acs.biochem.7b01306
[Indexed for MEDLINE]
Free PMC Article

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