Abstract
Universally present aminoacyl-tRNA synthetases (aaRSs) stringently recognize their cognate tRNAs and acylate them with one of the proteinogenic amino acids. However, some organisms possess aaRSs that deviate from the accurate translation of the genetic code and exhibit relaxed specificity toward their tRNA and/or amino acid substrates. Typically, these aaRSs are part of an indirect pathway in which multiple enzymes participate in the formation of the correct aminoacyl-tRNA product. The indirect cysteine (Cys)-tRNA pathway, originally thought to be restricted to methanogenic archaea, uses the unique O-phosphoseryl-tRNA synthetase (SepRS), which acylates the non-proteinogenic amino acid O-phosphoserine (Sep) onto tRNACys. Together with Sep-tRNA:Cys-tRNA synthase (SepCysS) and the adapter protein SepCysE, SepRS forms a transsulfursome complex responsible for shuttling Sep-tRNACys to SepCysS for conversion of the tRNA-bound Sep to Cys. Here, we report a comprehensive bioinformatic analysis of the diversity of indirect Cys encoding systems. These systems are present in more diverse groups of bacteria and archaea than previously known. Given the occurrence and distribution of some genes consistently flanking SepRS, it is likely that this gene was part of an ancient operon that suffered a gradual loss of its original components. Newly identified bacterial SepRS sequences strengthen the suggestion that this lineage of enzymes may not rely on the m1G37 identity determinant in tRNA. Some bacterial SepRSs possess an N-terminal fusion resembling a threonyl-tRNA synthetase editing domain, which interestingly is frequently observed in the vicinity of archaeal SepCysS genes. We also found several highly degenerate SepRS genes that likely have altered amino acid specificity. Cross-analysis of selenocysteine (Sec)-utilizing traits confirmed the co-occurrence of SepCysE and the Sec-utilizing machinery in archaea, but also identified an unusual O-phosphoseryl-tRNASec kinase fusion with an archaeal Sec elongation factor in some lineages, where it may serve in place of SepCysE to prevent crosstalk between the two minor aminoacylation systems. These results shed new light on the variations in SepRS and SepCysS enzymes that may reflect adaptation to lifestyle and habitat, and provide new information on the evolution of the genetic code.
Highlights
The essentially universal presence of twenty proteinogenic canonical amino acids in organismal proteomes is manifested by the existence of one or more aminoacyl-tRNA synthetase genes for each amino acid
We have previously shown that the two-step Cys biosynthesis and encoding pathway is not restricted to methanogenic archaea, but occurs in various archaeal as well as some bacterial clades (Mukai et al, 2017a)
This could indicate the absence of the transsulfursome complex (Figure 3) (Chen M. et al, 2017) in Asgard archaea, where SepRS might be detached from the SepCysE-Sep-tRNA:Cys-tRNA synthase (SepCysS) complex
Summary
The essentially universal presence of twenty proteinogenic canonical amino acids in organismal proteomes is manifested by the existence of one or more aminoacyl-tRNA synthetase (aaRS) genes for each amino acid These enzymes embody the major aminoacylation systems that generate by direct acylation the correctly charged (cognate) aminoacyl-tRNA (aa-tRNA) species for ribosomal protein synthesis (Yuan et al, 2008; Rubio Gomez and Ibba, 2020). The indirect translation systems depend on non-discriminating aaRSs that form non-cognate aa-tRNAs, whose misacylated amino acids are converted to the correct amino acid substrate by a set of different enzymes These minor aminoacylation systems are the sole route to asparaginyl (Asn)-, glutaminyl (Gln)-, cysteinyl (Cys)-tRNA in many prokaryotic organisms or organelles; the RNA-dependent selenocysteine (Sec) biosynthesis produces SectRNA in all three domains of life. The aaRS devoted to indirect Cys-tRNA synthesis, O-phosphoseryl-tRNA synthetase (SepRS), is unique in a sense that it does not ligate a proteinogenic amino acid, but the serine biosynthetic pathway intermediate (Helgadóttir et al, 2007) O-phosphoserine (Sep) to tRNACys
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
