Methylation of the nucleobases in RNA oligonucleotides mediates duplex-hairpin conversion |
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| Authors: | Micura R Pils W Höbartner C Grubmayr K Ebert M O Jaun B |
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| Affiliation: | Ronald Micura, Werner Pils, Claudia Höbartner, Karl Grubmayr, Marc-Olivier Ebert, and Bernhard Jaun |
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| Abstract: | We have systematically investigated the duplex to hairpin conversion of oligoribonucleotides under the aspect of nucleobase methylation. The first part of our study refers to the self-complementary sequence rCGCGAAUUCGCGA, which forms a stable Watson–Crick base paired duplex under various buffer conditions. It is shown that this sequence is forced to adopt a hairpin conformation if one of the central 6 nt is replaced by the corresponding methylated nucleotide, such as 1-methylguanosine N2,N2-dimethylguanosine, N6,N6-dimethyladenosine (m62A) or 3-methyluridine. On the other hand, the duplex structure is retained and even stabilized by replacement of a central nucleotide with N2-methylguanosine (m2G) or N4-methylcytidine. A borderline case is represented by N6-methyladenosine (m6A). Although generally a duplex-preserving modification, our data indicate that m6A in specific strand positions and at low strand concentrations is able to effectuate duplex–hairpin conversion. Our studies also include the ssu ribosomal helix 45 sequence motif, rGACCm2GGm62Am62AGGUC. In analogy, it is demonstrated that the tandem m62A nucleobases of this oligoribonucleotide prevent duplex formation with complementary strands. Therefore, it can be concluded that nucleobase methylations at the Watson–Crick base pairing site provide the potential not only to modulate but to substantially affect RNA structure by formation of different secondary structure motifs. |
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