InterPro domain: IPR038469

tRNA His molecules are unusual in having an extra 5' GMP residue (G(-1)) that, in eukaryotes, is added after transcription and RNase P cleavage. Incorporation of this G(-1) residue is a rare example of nucleotide addition occurring at an RNA 5' end in a normal phosphodiester linkage. In Saccharomyces cerevisiae, YGR024c (Thg1p) protein is responsible for this guanylyltransferase reaction [ 1 ]. It catalyses the guanylyltransferase step of G(-1) addition using a ppp-tRNA His substrate, and appears to catalyse the activation step using p-tRNA His and ATP. Thus, it catalyses phosphodiester bond formation at the 5' end of RNAs, formally in a 3'-5' direction [ 2 ].

Thg1 has also been shown to interact with the origin recognition complex and to be required for the G2/M phase transition [ 2 ], and to have polymerase activity [ 3 ]. The polymerase activity has been proposed to be the ancestral activity of this enzyme [ 4 ].

1. tRNAHis maturation: an essential yeast protein catalyzes addition of a guanine nucleotide to the 5' end of tRNAHis. Genes Dev. 17, 2889-901
2. The highly conserved tRNAHis guanylyltransferase Thg1p interacts with the origin recognition complex and is required for the G2/M phase transition in the yeast Saccharomyces cerevisiae. Eukaryotic Cell 4, 832-5
3. Template-dependent 3'-5' nucleotide addition is a shared feature of tRNAHis guanylyltransferase enzymes from multiple domains of life. Proc. Natl. Acad. Sci. U.S.A. 107, 674-9
4. tRNAHis guanylyltransferase catalyzes a 3'-5' polymerization reaction that is distinct from G-1 addition. Proc. Natl. Acad. Sci. U.S.A. 103, 8640-5