 Noncanonical base pair

A noncanonical base pair joins two nucleobases in an arrangement other than the standard Watson–Crick base pairing geometry. For RNA, the canonical Watson–Crick combinations are adenine–uracil and guanine–cytosine. Other combinations and contact geometries can contribute to an organized, functional RNA secondary structure; noncanonical does not mean an experimental mistake.

RNA base-pair geometry describes more than the two base letters. Which parts of the nucleobases contact each other, their relative orientation and their hydrogen bonds distinguish arrangements that a letter-only sequence description cannot specify. For a concrete structural example, solution NMR spectroscopy studies of GCAA and GAAA GNRA tetraloops identified a guanine–adenine base pair between the first and last loop residues, alongside other stabilizing contacts.^[ref]

An original counting example makes the distinction useful. A three-pair stem capped by a GAAA RNA tetraloop contains ten nucleotides: six in the stem and four in the loop. A contact between the loop's first guanine and last adenine can add a noncanonical base pair without adding any nucleotides or turning the four-residue loop into a different-length sequence. Sequence length, stem-pair count and the complete three-dimensional contact inventory answer different questions.

Conventions should be stated. Some RNA analyses include the common guanine–uracil wobble arrangement among their canonical pairs even though it differs from Watson–Crick geometry. The tetraloop survey, for example, explicitly adopts that broader convention.^[ref] Comparing reported counts therefore requires checking what each author counted as canonical.