RNA molecules that are assembled from the four standard nucleotides co
ntain a limited number of chemical functional groups, a characteristic
that is generally thought to restrict the potential for catalysis by
ribozymes. Although polypeptides carry a wider range of functional gro
ups, many contemporary protein-based enzymes employ coenzymes to augme
nt their capabilities. The coenzymes possess additional chemical moiet
ies that can participate directly in catalysis and thereby enhance cat
alytic function. In this work, we demonstrate a mechanism by which rib
ozymes can supplement their limited repertoire of functional groups th
rough RNA-catalyzed incorporation of various coenzymes and coenzyme an
alogues. The group I ribozyme of Tetrahymena thermophila normally medi
ates a phosphoester transfer reaction that results in the covalent att
achment of guanosine to the ribozyme. Here, a shortened version of the
ribozyme is shown to catalyze the self-incorporation of coenzymes and
coenzyme analogues, such as NAD(+) and dephosphorylated CoA-SH. Simil
ar ribozyme activities may have played an important role in the ''RNA
world,'' when RNA enzymes are thought to have maintained a complex met
abolism in the absence of proteins and would have benefited from the i
nclusion of additional functional groups.