Author
Wataru Yoshida, School of Bioscience and Biotechnology, Tokyo University of Technology
Taiji Oyama, Sales Division, JASCO Corporation
Keywords
G-quadruplex, intercalated motif, 5-methylcytosine, N6-methyladenine, Circular dichroism spectrum analysis
Abstract
Non-canonical nucleic acid structures such as triplexes, stem loops, D-loops, R-loops, cruciforms, G-quadruplexes (G4), and intercalated motifs (i-motifs) are formed in genomic DNA and RNA. In cells, non-canonical nucleic acid structures regulate biological processes; however, little is known regarding the mechanism via which the formation of non-canonical nucleic acid structures is regulated. In mammalian cells, the most common DNA and RNA modifications are 5-methylcytosine in CpG dinucleotides and N6-methyladenine, respectively. These modifications enhance stacking interactions with neighboring bases because the methyl group increases the molecular polarizability of the bases. In addition, 5-methylcytosine increases the base pairing energy of C-C+ formed in i-motif structures, and N6-methyladenine inhibits A-T base pairing, suggesting that these modifications affect the formation and thermal stability of noncanonical nucleic acid structures. Here, we describe the effect of 5-methylcytosine modification on VEGF G4 and i-motif structures, and that of N6-methyladenine modification on the G4 structure formed by GGA repeat RNA.