Abstract
Sulfur-containing transfer ribonucleic acids (tRNAs) are ubiquitous biomolecules found in all organisms that possess a variety of functions. For decades, their roles in processes such as translation, structural stability, and cellular protection have been elucidated and appreciated. These thionucleosides are found in all types of bacteria; however, their biosynthetic pathways are distinct among different groups of bacteria. Considering that many of the thio-tRNA biosynthetic enzymes are absent in Gram-positive bacteria, recent studies have addressed how sulfur trafficking is regulated in these prokaryotic species. Interestingly, a novel proposal has been given for interplay among thionucleosides and the biosynthesis of other thiocofactors, through participation of shared-enzyme intermediates, the functions of which are impacted by the availability of substrate as well as metabolic demand of thiocofactors. This review describes the occurrence of thio-modifications in bacterial tRNA and current methods for detection of these modifications that have enabled studies on the biosynthesis and functions of S-containing tRNA across bacteria. It provides insight into potential modes of regulation and potential evolutionary events responsible for divergence in sulfur metabolism among prokaryotes.
Highlights
Transfer ribonucleic acid is an essential facilitator in shuttling the genomic information between DNA and proteins
Detection and quantification of transfer ribonucleic acids (tRNAs) modification levels using liquid chromatography (LC) is performed on nucleosides isolated from purified tRNA samples
Investigation of pathways involved in the synthesis of thio-modifications of tRNA as well as discovery of new intermediates in these pathways were afforded through a combination of genomics, genetic, and biochemical approaches validated with spectroscopic and analytical methods for structural identification and quantification of these reaction products
Summary
Transfer ribonucleic acid (tRNA) is an essential facilitator in shuttling the genomic information between DNA and proteins. More than 100 RNA modifications have been discovered far, and the majority are found within tRNA molecules [3,4,5,6] Most of these “decorations” are derived from methylation, thiolation, and other more complex hypermodifications [7]. Pseudouridine (Ψ), a modification so abundant that it was identified as a “fifth nucleoside” in RNA, is an isomerization product resulting in a C–C rather than a N–C glycosyl bond of uridine which links between the base and sugar [8] Nucleoside thiolation is another widely occurring modification (Figure 1), including products such as 4-thiouridine (s4 U8), 2-thiouridine derivatives (xm s2 U34), 2-thiocytidine (s2 C32), 2-methylthio-N6 -isopentenyladenosine (ms i6 A37). Anticodon Stem Loop Modifications tRNA acts as an adapter molecule between the nucleic acid blueprint and the protein product by acts asacids an adapter moleculefor between the nucleic blueprint andThus, the protein product bringing amino to the ribosome incorporation into aacid growing peptide. The relevance of tRNA modifications in human disease is intriguing, as they highlight the functional importance of these modifications on a grand scale and provide attractive targets for therapies in disease
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