Novel RNA base pair with higher specificity using single selenium atom

• Published in: Nucleic acids research Vol. 40; no. 11; pp. 5171 - 5179
• Main Authors: Sun, Huiyan, Sheng, Jia, Hassan, Abdalla E A, Jiang, Sibo, Gan, Jianhua, Huang, Zhen
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-06-2012
• Subjects: Base Pair Mismatch; Base Pairing; Base pairs; Crystallography; DNA; Models, Molecular; non-coding RNA; Nucleic Acid Denaturation; Organophosphorus Compounds - chemical synthesis; Organoselenium Compounds - chemistry; Oxygen; Replication; RNA - chemistry; Selenium; Synthetic Biology and Chemistry; Transcription; Translation; Uridine; Uridine - analogs & derivatives; Uridine - chemical synthesis; Uridine - chemistry
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gks010

Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms. However, the wobble base pairs, where U in RNA (or T in DNA) pairs with G instead of A, might compromise the high specificity of the base pairing. The U/G wobble pairing is ubiquitous in RNA, especially in non-coding RNA. In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2-exo position of uridine and replacing the 2-exo oxygen with a selenium atom. We report here the first synthesis of the 2-Se-U-RNAs as well as the 2-Se-uridine ((Se)U) phosphoramidite. Our biophysical and structural studies of the (Se)U-RNAs indicate that this single atom replacement can indeed create a novel U/A base pair with higher specificity than the natural one. We reveal that the (Se)U/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair. This oxygen replacement with selenium offers a unique chemical strategy to enhance the base pairing specificity at the atomic level.