Non-Watson–Crick base pairs mediate specific
interactions responsible for RNA–RNA self-assembly
and RNA–protein recognition. An unambiguous and descriptive
nomenclature with well-defined and nonoverlapping parameters
is needed to communicate concisely structural information
about RNA base pairs. The definitions should reflect underlying
molecular structures and interactions and, thus, facilitate
automated annotation, classification, and comparison of
new RNA structures. We propose a classification based on
the observation that the planar edge-to-edge, hydrogen-bonding
interactions between RNA bases involve one of three distinct
edges: the Watson–Crick edge, the Hoogsteen edge,
and the Sugar edge (which includes the 2′-OH and
which has also been referred to as the Shallow-groove edge).
Bases can interact in either of two orientations with respect
to the glycosidic bonds, cis or trans
relative to the hydrogen bonds. This gives rise to 12 basic
geometric types with at least two H bonds connecting the
bases. For each geometric type, the relative orientations
of the strands can be easily deduced. High-resolution examples
of 11 of the 12 geometries are presently available. Bifurcated
pairs, in which a single exocyclic carbonyl or amino group
of one base directly contacts the edge of a second base,
and water-inserted pairs, in which single functional groups
on each base interact directly, are intermediate between
two of the standard geometries. The nomenclature facilitates
the recognition of isosteric relationships among base pairs
within each geometry, and thus facilitates the recognition
of recurrent three-dimensional motifs from comparison of
homologous sequences. Graphical conventions are proposed
for displaying non-Watson–Crick interactions on a
secondary structure diagram. The utility of the classification
in homology modeling of RNA tertiary motifs is illustrated.