Abstract
Various sulfur-containing biomolecules include iron–sulfur clusters that act as cofactors for enzymes, sulfur-containing vitamins such as thiamin, and sulfur-modified nucleosides in RNA, in addition to methionine and cysteine in proteins. Sulfur-containing nucleosides are post-transcriptionally introduced into tRNA molecules, where they ensure precise codon recognition or stabilization of tRNA structure, thereby maintaining cellular proteome integrity. Modulating sulfur modification controls the translation efficiency of specific groups of genes, allowing organisms to adapt to specific environments. The biosynthesis of tRNA sulfur nucleosides involves elaborate ‘sulfur trafficking systems’ within cellular sulfur metabolism and ‘modification enzymes’ that incorporate sulfur atoms into tRNA. This review provides an up-to-date overview of advances in our knowledge of the mechanisms involved. It covers the functions, biosynthesis, and biodegradation of sulfur-containing nucleosides as well as the reaction mechanisms of biosynthetic enzymes catalyzed by the iron–sulfur clusters, and identification of enzymes involved in the de-modification of sulfur atoms of RNA. The mechanistic similarity of these opposite reactions is discussed. Mutations in genes related to these pathways can cause human diseases (e.g., cancer, diabetes, and mitochondrial diseases), emphasizing the importance of these pathways.
Highlights
IntroductionSulfur is one of the six major elements (i.e., hydrogen, oxygen, carbon, nitrogen, phosphorus, and sulfur) accounting for 99% of living organisms
Various sulfur-containing biomolecules include iron–sulfur clusters that act as cofactors for enzymes, sulfur-containing vitamins such as thiamin, and sulfur-modified nucleosides in RNA, in addition to methionine and cysteine in proteins
Cysteine and methionine are the most well-known sulfur-containing molecules in living organisms, there are various other sulfur-containing biomolecules, including iron–sulfur clusters, that act as cofactors for enzymes, sulfur-containing vitamins such as thiamin, and sulfur-modified bases of RNA (Figure 1)
Summary
Sulfur is one of the six major elements (i.e., hydrogen, oxygen, carbon, nitrogen, phosphorus, and sulfur) accounting for 99% of living organisms. This flexibility makes it possible for sulfur to exist in a variety of forms and perform diverse functions in living organisms. These flexible chemical characteristics of sulfur have made experimental analysis difficult, but significant efforts have been made. The use of an oxygen-free experimental apparatus has become widespread, especially for molecules that are susceptible to oxidation Through these innovations, we know that for the biosynthesis of sulfur-modified bases of tRNA, organisms have evolved sophisticated systems to prevent secondary reactions and to allow only the desired reaction to proceed, which is essential for accurate protein synthesis [3]. For detailed structural aspects of RNA sulfurtransferases, please refer to an excellent review on the subject in [11]
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