Doing it in reverse: 3′-to-5′ polymerization by the Thg1 superfamily

The tRNA His guanylyltransferase (Thg1) family of enzymes comprises members from all three domains of life (Eucarya, Bacteria, Archaea). Although the initial activity associated with Thg1 enzymes was a single 39-to-59 nucleotide addition reaction that specifies tRNA His identity in eukaryotes, the discovery of a generalized base pair–dependent 39-to-59 polymerase reaction greatly expanded the scope of Thg1 family–catalyzed reactions to include tRNA repair and editing activities in bacteria, archaea, and organelles. While the identification of the 39-to-59 polymerase activity associated with Thg1 enzymes is relatively recent, the roots of this discovery and its likely physiological relevance were described ~30 yr ago. Here we review recent advances toward understanding diverse Thg1 family enzyme functions and mechanisms. We also discuss possible evolutionary origins of Thg1 family–catalyzed 39-to-59 addition activities and their implications for the currently observed phylogenetic distribution of Thg1-related enzymes in biology.