RNA molecules fold into specific three-dimensional shapes to perform struct
ural and catalytic functions. Large RNAs can form compact globular structur
es, but the chemical basis for close helical packing within these molecules
has been unclear. Analysis of transfer, catalysis, in vitro-selected and r
ibosomal RNAs reveal that helical packing predominantly involves the intera
ction of single-stranded adenosines with a helix minor groove. Using the Te
trahymena thermophila group I ribozyme, we show here that the near-perfect
shape complementarity between the adenine base and the minor groove allows
for optimal van der Waals contacts, extensive hydrogen bonding and hydropho
bic surface burial, creating a highly energetically favorable interaction.
Adenosine is recognized in a chemically similar fashion by a combination of
protein and RNA C components in the ribonucleoprotein core of the signal r
ecognition particle. These results provide a thermodynamic explanation for
the noted abundance of conserved adenosines within the unpaired regions of
RNA secondary structures.