Pseudouridine Modifications in Transfer RNA and tRNA Pseudouridine Synthases

Among the various modifications found in transfer RNAs, pseudouridine occurs the most frequently in all organisms and is also found in other RNA species including ribosomal, messenger, small nuclear, small nucleolar, and transfer-messenger RNA. Since the first gene encoding a tRNA pseudouridine synthase (truA) was discovered in 1978, many pseudouridine synthases have been identified, some of which are specific for one site in tRNA, while others act at multiple sites. Furthermore, some enzymes catalyze pseudouridine modification of not only tRNA but also ribosomal RNA and small nuclear RNA or messenger RNA. The functions of pseudouridine in tRNA are diverse, from contributing to the stabilization of tRNA structure to having an essential role in accurate protein synthesis (deficiency induces a frameshift in some cases). Some pseudouridine synthases also function as RNA chaperones. In this review, I summarize the reaction mechanism and functions of pseudouridine synthases with reference to the six pseudouridine synthase families, including similarities and variations in domain structures, motifs, and target uracil bases. I also characterize individual enzymes and highlight recently revealed links between pseudouridine/pseudouridine synthases and viral infections and human diseases.