GpU dinucleotide platform, the smallest unit with key RNA structural features

RNA has three salient structural features (compared to DNA): it contains the ribose (not deoxyribose) sugar, it has the uracil (not thymine) base, and it is normally single (not double)-stranded. The O2′(G)…O2P(U) H-bond stabilized GpU dinucleotide platform may turn out to be the smallest unit with all those RNA hallmarks.

First, it must have the guanosine ribose to have the 2′-hydroxyl group form the O2′(G)…O2P(U) H-bond.

Second, the methyl group in position 5 of thymine would cause steric clash with guanosine, thus disrupting the N2(G)…O4(U) base-base H-bond to form the GpU dinucleotide platform.

Third, a dinucleotide, by definition, is single-standed. The two H-bonds, plus the covalent linkage, makes the GpU platform extremely rigid (see Figure 1 of our 2010 NAR paper).

Moreover, the GpU platform is directional: swapping the two bases while keeping the sugar-phosphate backbone fixed does not allow for a base-base H-bond, thus no UpG dinucleotide platform.

It worth noting that state-of-the-art quantum chemistry calculations have verified the importance of the O2′(G)…O2P(U) H-bond in stabilizing the GpU dinucleotide platform.

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