title: Structural insights of non-canonical U*U pair and Hoogsteen interaction probed with Se atom.
abstract: Unlike DNA, in addition to the 2'-OH group, uracil nucleobase and its modifications play essential roles in structure and function diversities of non-coding RNAs. Non-canonical U•U base pair is ubiquitous in non-coding RNAs, which are highly diversified. However, it is not completely clear how uracil plays the diversifing roles. To investigate and compare the uracil in U-A and U•U base pairs, we have decided to probe them with a selenium atom by synthesizing the novel 4-Se-uridine ((Se)U) phosphoramidite and Se-nucleobase-modified RNAs ((Se)U-RNAs), where the exo-4-oxygen of uracil is replaced by selenium. Our crystal structure studies of U-A and U•U pairs reveal that the native and Se-derivatized structures are virtually identical, and both U-A and U•U pairs can accommodate large Se atoms. Our thermostability and crystal structure studies indicate that the weakened H-bonding in U-A pair may be compensated by the base stacking, and that the stacking of the trans-Hoogsteen U•U pairs may stabilize RNA duplex and its junction. Our result confirms that the hydrogen bond (O4(…)H-C5) of the Hoogsteen pair is weak. Using the Se atom probe, our Se-functionalization studies reveal more insights into the U•U interaction and U-participation in structure and function diversification of nucleic acids.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA and Department of Biology, Brookhaven National Laboratory, Upton, NY, 11973, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Sheng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gan
authors.forename: Alexei S
authors.initials: AS
authors.lastname: Soares
authors.forename: Jozef
authors.initials: J
authors.lastname: Salon
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
mesh_terms: D020029:Base Pairing; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D022661:RNA, Untranslated / Q000138:chemical synthesis / Q000737:chemistry*; D012643:Selenium / Q000737:chemistry*; D014498:Uracil / Q000737:chemistry*; D014529:Uridine / Q000737:chemistry
chemical_list: D009943:Organophosphorus Compounds; D022661:RNA, Untranslated; C434331:phosphoramidite; D014498:Uracil; D012643:Selenium; D014529:Uridine