Crystal structure of a reverse polymerase

Abstract

The primary transcripts of transfer RNA (tRNA) molecules undergo extensive processing and chemical modification to become functional components of the protein synthesis apparatus. Some of these reactions are common to all tRNAs in a particular cell, whereas others are specific to a subset of the species or even to just a single amino-acid–accepting class (1). In some organisms the maturation of histidine-specific tRNAs (tRNAHis) includes the unique addition of guanosine (G−1) to the 5′ terminus of tRNA (2). This G−1 addition step is a phosphodiester bond formation reaction that operates in a unique 3′-5′ direction, opposite to all conventional DNA and RNA polymerases. In PNAS, Hyde et al. (3) unveil crystal structures of a Thg1 enzyme that catalyzes G−1 addition. The structures show that the catalytic domain of Thg1 shares both a common architecture and a two-metal ion-dependent mechanism with canonical 5′-3′ DNA polymerases. These remarkable findings open new vistas in tRNA enzymology and the evolution of nucleic acid polymerases.