Biogenesis and Functions of Thio‑Compounds in Transfer RNA: Comparison of Bacterial and Eukaryotic Thiolation Machineries
Ken-ichi Noma, Naoki Shigi and Tsutomu Suzuki
Sulfur is an essential element for all living organisms. Several modified nucleosides containing sulfur atoms are found in tRNA molecules, namely 2‑thiocytidine (s2C), 2‑thiouridine (s2U) derivatives, 4‑thiouridine (s4U) and 2‑methylthioadenosine (ms2A) derivatives. Especially, 2‑thio group of s2U derivatives is known to ensure accurate deciphering the genetic code and stabilization of tRNA structure. Recent studies reveal that in many cases cysteine desulfurase catalyzes the generation of persulfide sulfur from cysteine, which is then transferred to various pathways in cellular sulfur trafficking, including biogenesis of an iron‑sulfur cluster and formation of various sulfur‑containing metabolites and thio‑containing RNAs. Identification of sulfur mediators and thiouridylases from E. coli, Thermus thermophilus and Saccharomyces cerevisiae has revealed species‑specific sulfur‑relay systems for 2‑thiouridine formation. In E. coli, multiple sulfur mediators sequentially relay the sulfur atom based on persulfide chemistry while in T. thermophilus and S. cerevisiae, the activated sulfur is relayed through a ubiquitination‑like chemical reaction that involves a thiocarboxylated intermediate.