The major difference between RNA and DNA is the presence of a hydroxyl group at the 2-position of the ribose sugar in RNA (illustration, right). This group makes the molecule less stable because, when not constrained in a double helix, the 2 hydroxyl can chemically attack the adjacent phosphodiester bond to cleave the phosphodiester backbone. The hydroxyl group also forces the ribose into the C3-endo sugar conformation unlike the C2-endo conformation of the deoxyribose sugar in DNA. This forces an RNA double helix to change from a B-DNA structure to one more closely resembling A-DNA.
RNA also uses a different set of bases than DNA—adenine, guanine, cytosine and uracil, instead of adenine, guanine, cytosine and thymine. Chemically, uracil is similar to thymine, differing only by a methyl group, and its production requires less energy. In terms of base pairing, this has no effect. Adenine readily binds uracil or thymine. Uracil is, however, one product of damage to cytosine that makes RNA particularly susceptible to mutations that can replace a GC base pair with a GU (wobble) or AU base pair.
RNA is thought to have preceded DNA, because of their ordering in the biosynthetic pathways. The deoxyribonucleotides used to make DNA are made from ribonucleotides, the building blocks of RNA, by removing the 2'-hydroxyl group. As a consequence, a cell must have the ability to make RNA before it can make DNA.