Why is DNA polymorphic while RNA is not?

Abstract

In DNA, the base-sugar hydrophobic interactions between the 2'-methylene group of the 2'-deoxyribose sugar and the base (H6 in pyrimidines and H8 in purines) on the 3'-side appear to act as a ball joint and facilitate the A-DNA c, B-DNA conformational interconversion by lowering the pseudorotational barrier. These and other sugar-base interactions coupled with the inherently more flexible 2'-deoxyribofuranose ring allow DNA to occur in a variety of polymorphic helical states. In contrast, the 2'-hydroxyl group in RNA not only sterically disfavors the B-type structure, but the inherently less flexible ribofuranose ring is further stabilized in the A-type structure by intramolecular hydrogen-bonded water bridge between the 2'-OH group and the base (02 in pyrimidines and N3 in purines).. This lack of flexibility of RNA dictates that DNA-RNA hybrid structures assume the A-type helix.DNA is found to occur in a number of polymorphic structural forms [l]. Besides the familiar right-handed A-and B-type double helical structures [2-51, the possibility of left-handed Z-type structures [6] has recently emerged. The capacity of DNA to adopt these and possibly other conformational structures in local regions has provided an attractive mechanism for understanding the way genes are turned on and off. On the other hand, RNA is less flexible than its cousin DNA and has been found so far to display only the A-type structure. It appears that nature has designed these differences in DNA and RNA for their separate biological roles.Chemically, RNA differs from DNA in that its main chain consists of ribofuranose sugars rather than 2'-deoxyribofuranose sugars. In addition, the base thymine in DNA occurs in the demethylated form, uridine, in RNA. In this article, we investigate the effect of these two chemical differences, one in the main chain and the other in a side chain base, on the overall structural and conformational properties of DNA and RNA. Some Structural Features of A-, B-, and Z-DNAIn both A-DNA and B-DNA, a 2'-methylene hydrogen atom of the sugar is in van der Walls contact with the base on the 3'-side ( hydrophobic interactions can be visualized as a mechanical ball joint which aids the "smooth" C3'-endo (A-DNA) ff C2'-endo (B-DNA) interconversion.* Thus, the flexibility of the sugar (or pseudorotational mobility) is related not only to the glycosyl torsion angle of the attached base (C3'-endo, low x; and C2'-endo, high x) [8] but also is transmitted to the base on the 3'-side. When the 3'-base is a thymine, this base-sugar "stacking" interaction is augmented by the involvement of the 5-methyl group (Fig. 2). It would then appear that the methylene-base(H61H8) and also the methylene-methyl (of T) interactions would tend to reduce the sugar-pucker interconversion barrier and contribute to the flexibility of DNA, particularly in AT-rich regions [lo].*The pseudoration barriers €or the interconversion have been variously estimated for the ribose and deoxyribose systems. While there is still no single value for these ba...

Activated Ribonucleotides Undergo a Sugar Pucker Switch upon Binding to a Single-Stranded RNA Template

“…The switch of the ribonucleotide monomers in the bound state to a 3′- endo sugar pucker is necessary for the discontinuous strand to form the sterically favored A-type duplex. 26 The change in monomer conformation upon template binding suggests that monomers that are preorganized in the 3′- endo conformation should bind more tightly and polymerize more efficiently. Thus, 2-thio-UMP, which exists in a 3′- endo conformation when free in solution, 27 should be a better substrate for nonenzymatic template-directed polymerization than standard UMP.…”

“…The observed conformational switch can be rationalized in terms of the assembly of adjacent monomers on the template strand to form a pseudoduplex structure in which one strand is discontinuous and consists of noncovalently linked monomers. Such a prepolymerization structure cannot form a B-type duplex because of the steric clash between the monomer 2′-hydroxyls and the phosphodiester backbone (see Figure 4 of ref ). The switch of the ribonucleotide monomers in the bound state to a 3′- endo sugar pucker is necessary for the discontinuous strand to form the sterically favored A-type duplex .…”

“…Such a prepolymerization structure cannot form a B-type duplex because of the steric clash between the monomer 2′-hydroxyls and the phosphodiester backbone (see Figure 4 of ref ). The switch of the ribonucleotide monomers in the bound state to a 3′- endo sugar pucker is necessary for the discontinuous strand to form the sterically favored A-type duplex . The change in monomer conformation upon template binding suggests that monomers that are preorganized in the 3′- endo conformation should bind more tightly and polymerize more efficiently.…”