Structures and Energetics of Four Adjacent G·U Pairs That Stabilize an RNA Helix
Year: 2015
Type: article
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: Xiaobo Gu, Blaine H. M. Mooers, Leonard M. Thomas, Joshua Malone, Steven Harris, Susan J. Schroeder
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Oklahoma Center for the Advancement of Science and Technology, Francis Crick Institute, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Office of Integrative Activities, Division of Molecular and Cellular Biosciences
Awards: WIDE-BORE 9.4 TESLA NMR SPECTROMETER FOR UW-MADISON, Upgrade of the NMRFAM 750 MHz NMR Spectrometer, The role of non-canonical base pairs in RNA editing, National Biomedical NMR Resource at Madison, National Biological NMR Facility at Madison, Integrated state-of-the-art LC-MS/NMR system for the University of Wisconsin, Development of 750 MHz Spectroscopy at the National Magnetic Resonance Facility at Madison., G5268575721, National Biomedical NMR Resource at Madison, CONSOLE UPGRADES FOR NMR FACILITY, NMR Spectrometer System Optimized for Direct 13C or 15N Detection, High Field NMR System for Metabolic Imaging of Human Disease, 900 MHz NMR Spectrometer Biomolecular Investigations, Oklahoma COBRE in Structural Biology, Predicting viral RNA structure, function and drug targets, G8690412431
OpenAlex ID: W2267583007