2-Thiouridine formation in Escherichia coli: a critical review

Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability, and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in prokaryotes and eukaryotes. The s² group of s²U34 stabilizes anticodon structure, confers ribosome-binding ability to tRNA, and improves reading frame maintenance. In particular, specific enzymes catalyze the biosynthesis of sulfur-containing nucleosides of s²U34, such as the L-cysteine desulfurase IscS and the tRNA thiouridylase MnmA in Escherichia coli. Until recently, the mechanism of sulfur transfer in E. coli was considered to involve persulfide chemistry; however, a newly proposed mechanism suggests the involvement of a [4Fe-4S] cluster bound to MnmA. This review provides a critical appraisal of recent evidence for [4Fe-4S]-dependent or [4Fe-4S]-independent tRNA thiolation in 2-thiouridine formation.