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Structural insights into RNA duplexes with multiple 2΄-5΄-linkages

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...

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Detalles Bibliográficos
Autores principales: Shen, Fusheng, Luo, Zhipu, Liu, Hehua, Wang, Rui, Zhang, Shenglong, Gan, Jianhua, Sheng, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389462/
https://www.ncbi.nlm.nih.gov/pubmed/28034958
http://dx.doi.org/10.1093/nar/gkw1307
Descripción
Sumario: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.