Abstract
All nucleic acids in cells are subject to post-transcriptional chemical modifications. These are catalyzed by a myriad of enzymes with exquisite specificity and that utilize an often-exotic array of chemical substrates. In no molecule are modifications more prevalent than in transfer RNAs. In the present document, we will attempt to take a chemical rollercoaster ride from prebiotic times to the present, with nucleoside modifications as key players and tRNA as the centerpiece that drove the evolution of biological systems to where we are today. These ideas will be put forth while touching on several examples of tRNA modification enzymes and their modus operandi in cells. In passing, we submit that the choice of tRNA is not a whimsical one but rather highlights its critical function as an essential invention for the evolution of protein enzymes.
Highlights
The Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA
While missense mutations caused by Transfer RNAs (tRNAs) mischarging or inaccurate decoding can be detrimental for protein activity or structure, frameshift mutations are far more destructive to overall protein synthesis and are often fatal [35,51,52,91,92,93,94,95,96,97,98]
Along with the active site, we found that ADAT2 in T. brucei has acquired a lysine and arginine-rich tRNA binding domain, named the KR-domain, at its C-terminal end [130]
Summary
Before there could be RNA, nucleotides had to exist. This is an inescapable dictum leading to the advent of the RNA world; tRNA included. Any discussions of the role modifications played at the beginning of life and what roles they play today, including their evolution and prevalence in tRNA, has to forcibly touch on what was there before life began. Such discussions inevitably start with what was possible in terms of prebiotic chemistry and the formation of nucleosides. Pyrimidine derivatives were generated most notably 2-thiolated uridine and cytidine [14] This has led to several ideas as to what roles such modified nucleotides may have played in early life evolution. We will discuss what roles, beyond chemical diversity to increase catalytic capabilities, these modifications may have played while highlighting the functions that some of the most ancient modifications still play today
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