The human ortholog of archaeal Pus10 produces pseudouridine 54 in select tRNAs where its recognition sequence contains a modified residue [ARTICLE]

The nearly conserved U54 of tRNA is mostly converted to a version of ribothymidine (T) in Bacteria and eukaryotes and to a version of pseudouridine () in Archaea. Conserved U55 is nearly always modified to 55 in all organisms. Orthologs of TrmA and TruB that produce T54 and 55, respectively, in Bacteria and eukaryotes are absent in Archaea. Pus10 produces both 54 and 55 in Archaea. Pus10 orthologs are found in nearly all sequenced archaeal and most eukaryal genomes, but not in yeast and bacteria. This coincides with the presence of 54 in most archaeal tRNAs and some animal tRNAs, but its absence from yeast and bacteria. Moreover, 54 is found in several tRNAs that function as primers for retroviral DNA synthesis. Previously, no eukaryotic tRNA 54 synthase had been identified. We show here that human Pus10 can produce 54 in select tRNAs, including tRNA^Lys3, the primer for HIV reverse transcriptase. This synthase activity of Pus10 is restricted to the cytoplasm and is distinct from nuclear Pus10, which is known to be involved in apoptosis. The sequence GUUCAm¹AAUC (m¹A is 1-methyladenosine) at position 53–61 of tRNA along with a stable acceptor stem results in maximum 54 synthase activity. This recognition sequence is unique for a synthase in that it contains another modification. In addition to 54, SF9 cells-derived recombinant human Pus10 can also generate 55, even in tRNAs that do not contain the 54 synthase recognition sequence. This activity may be redundant with that of TruB.

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