U6 RNA contains two regions that are essential for proper splicing of
nuclear precursor messenger RNA (pre-mRNA). A comparison of putative s
econdary structures of the U6-U4 RNA complexes from different phyla re
vealed a conserved domain that is similar to the catalytic hammerhead
RNA motif. Although no catalytic activity was detected in the mammalia
n U6-U4 RNA complexes, two nucleotide changes in U6 RNA and one in U4
RNA conferred cleavage activity to the complex. Furthermore, the highl
y conserved domain of the wild-type complex, without the accompanying
flanking regions, cleaved an RNA substrate and exhibited other charact
eristics of the hammerhead ribozyme. The possible involvement of this
structure in pre-mRNA splicing is also discussed.