Transfer RNA Modification Enzymes with a Thiouridine Synthetase, Methyltransferase and Pseudouridine Synthase (THUMP) Domain and the Nucleosides They Produce in tRNA

Abstract

The existence of the thiouridine synthetase, methyltransferase and pseudouridine synthase (THUMP) domain was originally predicted by a bioinformatic study. Since the prediction of the THUMP domain more than two decades ago, many tRNA modification enzymes containing the THUMP domain have been identified. According to their enzymatic activity, THUMP-related tRNA modification enzymes can be classified into five types, namely 4-thiouridine synthetase, deaminase, methyltransferase, a partner protein of acetyltransferase and pseudouridine synthase. In this review, I focus on the functions and structures of these tRNA modification enzymes and the modified nucleosides they produce. Biochemical, biophysical and structural studies of tRNA 4-thiouridine synthetase, tRNA methyltransferases and tRNA deaminase have established the concept that the THUMP domain captures the 3′-end of RNA (in the case of tRNA, the CCA-terminus). However, in some cases, this concept is not simply applicable given the modification patterns observed in tRNA. Furthermore, THUMP-related proteins are involved in the maturation of other RNAs as well as tRNA. Moreover, the modified nucleosides, which are produced by the THUMP-related tRNA modification enzymes, are involved in numerous biological phenomena, and the defects of genes for human THUMP-related proteins are implicated in genetic diseases. In this review, these biological phenomena are also introduced.

Beyond the Anticodon: tRNA Core Modifications and Their Impact on Structure, Translation and Stress Adaptation

“…The majority of the basic knowledge concerning the impact of core modifications on tRNA structure was mainly discovered towards the end of the last century and has been comprehensively reviewed and discussed elsewhere [ 16 , 17 , 45 , 46 , 47 , 48 ]. We provide here only a concise overview of these fundamentals, which are at the root of all local and global molecular changes associated with the introduction of modifications.…”

RudS: Bacterial Desulfidase Responsible for tRNA 4-Thiouridine De-modification

“…ThiI, initially identified as an enzyme involved in thiamine biosynthesis in E. coli, is typically regarded as the primary biosynthetic enzyme for s4U (24). In fact, enzymes responsible for s4U synthesis vary across species, exhibiting differing structural features and sulfur transfer mechanisms (9,(25)(26)(27)(28). Among sulfur-containing tRNA modifications, s4U stands out for its unique susceptibilities, including being a target for UV-A irradiation, which can impair translation by stalling aminoacylation of cross-linked tRNAs (29,30).…”