1. INTRODUCTION 399

2. DEFINITIONS 401

3. CIS BASEPAIRS 410

3.1 Cis Watson–Crick/Watson–Crick 410

3.2 Wobble pairings 411

3.3 Cis Watson–Crick/Hoogsteen pairings 416

3.4 Bifurcated pairings 417

3.5 Cis open and water-inserted 421

4. TRANS BASEPAIRS 423

4.1 Trans Watson–Crick/Watson–Crick 423

4.2 Trans wobble pairs 424

4.3 Trans Watson–Crick/Hoogsteen pairs 424

4.4 Trans Hoogsteen/Hoogsteen pairs 430

4.5 Trans bifurcated pairings 432

5. SHALLOW-GROOVE PAIRINGS 432

5.1 Hoogsteen/Shallow-groove pairs 433

5.2 Watson–Crick/Shallow-groove pairings 438

5.3 Shallow-groove/Shallow-groove pairings 440

6. SIDE-BY-SIDE BASES 446

7. DEFINING A LIBRARY OF ISOSTERIC PAIRINGS 446

8. CONCLUSIONS 451

9. ACKNOWLEDGEMENTS 452

10. REFERENCES 452

RNA molecules fold into a bewildering variety of complex 3D structures. Almost every new RNA structure obtained at high resolution reveals new, unanticipated structural motifs, which we are rarely able to predict at the current stage of our theoretical understanding. Even at the most basic level of specific RNA interactions – base-to-base pairing – new interactions continue to be uncovered as new structures appear. Compilations of possible non-canonical base-pairing geometries have been presented in previous reviews and monographs (Saenger, 1984; Tinoco, 1993). In these compilations, the guiding principle applied was the optimization of hydrogen-bonding. All possible pairs with two standard H-bonds were presented and these were organized according to symmetry or base type. However, many of the features of RNA base-pairing interactions that have been revealed by high-resolution crystallographic analysis could not have been anticipated and, therefore were not incorporated into these compilations. These will be described and classified in the present review. A recently presented approach for inferring basepair geometry from patterns of sequence variation (Gautheret & Gutell, 1997) relied on the 1984 compilation of basepairs (Saenger, 1984), and was extended to include all possible single H-bond combinations not subject to steric clashes. Another recent review may be consulted for a discussion of the NMR spectroscopy and thermodynamic effects of non-canonical (‘mismatched’) RNA basepairs on duplex stability (Limmer, 1997).