title: Structural insights into RNA duplexes with multiple 2΄-5΄-linkages.
abstract: 2΄-5΄-linked RNAs play important roles in many biological systems. In addition, the mixture of 2΄-5΄ and 3΄-5΄ phosphodiester bonds have emerged as a plausible structural element in prebiotic RNAs. Toward our mechanistic studies of RNA folding and structures with heterogeneous backbones, we recently reported two crystal structures of a decamer RNA duplex containing two and six 2΄-5΄-linkages, showing how RNA duplexes adjust the structures to accommodate these non-canonical linkages (Proc. Natl. Acad. Sci. USA, 2014, 111, 3050-3055). Herein, we present two additional high-resolution crystal structures of the same RNA duplex containing four and eight 2΄-5΄-linkages at different positions, providing new insights into the effects of these modifications and a dynamic view of RNA structure changes with increased numbers of 2΄-5΄-linkages in the same duplex. Our results show that the local structural perturbations caused by 2΄-5΄ linkages can be distributed to nearly all the nucleotides with big ranges of changes in different geometry parameters. In addition, hydration pattern and solvation energy analysis indicate less favorable solvent interactions of 2΄-5΄-linkages comparing to the native 3΄-5΄-linkages. This study not only promotes our understanding of RNA backbone flexibility, but also provides a knowledge base for studying the biochemical and prebiotic significance of RNA 2΄-5΄-linkages.
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.|The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Shen
authors.affiliation: Synchrotron Radiation Research Section, MCL National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Zhipu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Hehua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.|The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, New York Institute of Technology, New York, NY 10023, USA.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gan
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA.|The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Sheng
mesh_terms: D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry; D012330:RNA, Double-Stranded / Q000737:chemistry*
chemical_list: D009711:Nucleotides; D012330:RNA, Double-Stranded