title: 2-Thiouracil deprived of thiocarbonyl function preferentially base pairs with guanine rather than adenine in RNA and DNA duplexes.
abstract: 2-Thiouracil-containing nucleosides are essential modified units of natural and synthetic nucleic acids. In particular, the 5-substituted-2-thiouridines (S2Us) present in tRNA play an important role in tuning the translation process through codon-anticodon interactions. The enhanced thermodynamic stability of S2U-containing RNA duplexes and the preferred S2U-A versus S2U-G base pairing are appreciated characteristics of S2U-modified molecular probes. Recently, we have demonstrated that 2-thiouridine (alone or within an RNA chain) is predominantly transformed under oxidative stress conditions to 4-pyrimidinone riboside (H2U) and not to uridine. Due to the important biological functions and various biotechnological applications for sulfur-containing nucleic acids, we compared the thermodynamic stabilities of duplexes containing desulfured products with those of 2-thiouracil-modified RNA and DNA duplexes. Differential scanning calorimetry experiments and theoretical calculations demonstrate that upon 2-thiouracil desulfuration to 4-pyrimidinone, the preferred base pairing of S2U with adenosine is lost, with preferred base pairing with guanosine observed instead. Therefore, biological processes and in vitro assays in which oxidative desulfuration of 2-thiouracil-containing components occurs may be altered. Moreover, we propose that the H2U-G base pair is a suitable model for investigation of the preferred recognition of 3'-G-ending versus A-ending codons by tRNA wobble nucleosides, which may adopt a 4-pyrimidinone-type structural motif.
authors.affiliation: Institute of Organic Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Sochacka
authors.affiliation: International Institute of Molecular and Cell Biology, Ks. J. Trojdena 4, 02-109 Warsaw, Poland.
authors.forename: Roman H
authors.initials: RH
authors.lastname: Szczepanowski
authors.affiliation: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Cypryk
authors.affiliation: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Sobczak
authors.affiliation: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Janicka
authors.affiliation: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
authors.forename: Karina
authors.initials: K
authors.lastname: Kraszewska
authors.affiliation: Institute of Organic Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Bartos
authors.affiliation: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Chwialkowska
authors.affiliation: Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland bnawrot@cbmm.lodz.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nawrot
mesh_terms: D000225:Adenine / Q000737:chemistry; D020029:Base Pairing; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006147:Guanine / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry* / Q000235:genetics; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D013889:Thiouracil / Q000737:chemistry*; D013891:Thiouridine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: C105273:2-thiouridine; D009692:Nucleic Acid Heteroduplexes; D013891:Thiouridine; D013889:Thiouracil; D006147:Guanine; D012313:RNA; D004247:DNA; D000225:Adenine