title: Effects of N2,N2-dimethylguanosine on RNA structure and stability: crystal structure of an RNA duplex with tandem m2 2G:A pairs.
abstract: Methylation of the exocyclic amino group of guanine is a relatively common modification in rRNA and tRNA. Single methylation (N(2)-methylguanosine, m(2)G) is the second most frequently encountered nucleoside analog in Escherichia coli rRNAs. The most prominent case of dual methylation (N(2),N(2)-dimethylguanosine, m(2) (2)G) is found in the majority of eukaryotic tRNAs at base pair m(2) (2)G26:A44. The latter modification eliminates the ability of the N(2) function to donate in hydrogen bonds and alters its pairing behavior, notably vis-à-vis C. Perhaps a less obvious consequence of the N(2),N(2)-dimethyl modification is its role in controlling the pairing modes between G and A. We have determined the crystal structure of a 13-mer RNA duplex with central tandem m(2) (2)G:A pairs. In the structure both pairs adopt an imino-hydrogen bonded, pseudo-Watson-Crick conformation. Thus, the sheared conformation frequently seen in tandem G:A pairs is avoided due to a potential steric clash between an N(2)-methyl group and the major groove edge of A. Additionally, for a series of G:A containing self-complementary RNAs we investigated how methylation affects competitive hairpin versus duplex formation based on UV melting profile analysis.
authors.affiliation: Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Pallan
authors.forename: Christoph
authors.initials: C
authors.lastname: Kreutz
authors.forename: Silvia
authors.initials: S
authors.lastname: Bosio
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
authors.forename: Martin
authors.initials: M
authors.lastname: Egli
mesh_terms: D000225:Adenine / Q000737:chemistry*; D020137:Base Pair Mismatch; D020029:Base Pairing; D018360:Crystallography, X-Ray; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D008745:Methylation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000528:radiation effects; D020871:RNA Stability / Q000528:radiation effects; D044366:Transition Temperature; D014466:Ultraviolet Rays
chemical_list: D006151:Guanosine; C008940:N(2),N(2)-dimethylguanosine; D012313:RNA; D000225:Adenine
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