tRNA maturation: RNA polymerization without a nucleic acid template

The CCA-adding enzyme, which builds and repairs the 3 ′ terminal CCA sequence of tRNA, is the only RNA polymerase that can synthesize a defined nucleotide sequence without using a nucleic acid template. New cocrystal structures tell us how this remarkable enzyme works. The 3 ′ terminal sequence of all mature tRNAs in all organisms is CCA. In those eubacteria where all tRNA genes encode CCA, the CCA-adding enzyme repairs mature tRNAs whose 3 ′ ends have succumbed to nuclease attack; in other organisms, where most or all tRNA genes do not encode CCA, the enzyme builds or repairs the CCA sequence by adding one nucleotide at a time. Thus this 45 kDa enzyme, described by the late crystallographer Paul Sigler as “the smartes