title: Structures and Energetics of Four Adjacent G·U Pairs That Stabilize an RNA Helix.
abstract: Consecutive G·U base pairs inside RNA helices can be destabilizing, while those at the ends of helices are thermodynamically stabilizing. To determine if this paradox could be explained by differences in base stacking, we determined the high-resolution (1.32 Å) crystal structure of (5'-GGUGGCUGUU-3')2 and studied three sequences with four consecutive terminal G·U pairs by NMR spectroscopy. In the crystal structure of (5'-GGUGGCUGUU-3')2, the helix is overwound but retains the overall features of A-form RNA. The penultimate base steps at each end of the helix have high base overlap and contribute to the unexpectedly favorable energetic contribution for the 5'-GU-3'/3'-UG-5' motif in this helix position. The balance of base stacking and helical twist contributes to the positional dependence of G·U pair stabilities. The energetic stabilities and similarity to A-form RNA helices suggest that consecutive G·U pairs would be recognized by RNA helix binding proteins, such as Dicer and Ago. Thus, these results will aid future searches for target sites of small RNAs in gene regulation.
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Microbiology and Plant Biology, University of Oklahoma , Norman, Oklahoma 73019, United States.|Department of Biochemistry and Molecular Biology and ∥Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Microbiology and Plant Biology, University of Oklahoma , Norman, Oklahoma 73019, United States.|Department of Biochemistry and Molecular Biology and ∥Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Blaine H M
authors.initials: BH
authors.lastname: Mooers
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Microbiology and Plant Biology, University of Oklahoma , Norman, Oklahoma 73019, United States.|Department of Biochemistry and Molecular Biology and ∥Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Thomas
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Microbiology and Plant Biology, University of Oklahoma , Norman, Oklahoma 73019, United States.|Department of Biochemistry and Molecular Biology and ∥Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Malone
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Microbiology and Plant Biology, University of Oklahoma , Norman, Oklahoma 73019, United States.|Department of Biochemistry and Molecular Biology and ∥Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Harris
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Microbiology and Plant Biology, University of Oklahoma , Norman, Oklahoma 73019, United States.|Department of Biochemistry and Molecular Biology and ∥Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Schroeder
mesh_terms: D020029:Base Pairing; D018360:Crystallography, X-Ray; D006147:Guanine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D014498:Uracil / Q000737:chemistry*
chemical_list: D014498:Uracil; D006147:Guanine; D012313:RNA