“…tRNA modifications are generally categorized into two regions of tRNA structure: body modifications and anticodon stem–loop (ACL) modifications. , Modifications to the ACL frequently aid in the efficiency or fidelity of translation, while body modifications have been more challenging to understand due to their distant location from the site of codon–anticodon interaction. Body modifications generally exhibit a more indirect yet important role in tRNA folding and stability, while also playing a part in tRNA quality control to ensure a functional pool of tRNA molecules is maintained. , In S. cerevisiae , there are 10 chemically unique modifications found in the tRNA body region while the ACL region contains the majority of remaining tRNA modifications. , The chemical diversity of tRNA nucleotide base and ribose modifications is vast, ranging from addition of relatively “simple” chemical groups via acetylation or methylation, to more profound chemical and structural changes with complex modifications such as queuosine or wybutosine. , Base methylation, the focus of this Account, comprises 8 chemically unique modifications of cytoplasmic tRNAs in S. cerevisiae : 1-methylguanosine (m 1 G), 2-methylguanosine (m 2 G), N 2 , N 2 -dimethylguanosine (m 2,2 G), 7-methylguanosine (m 7 G), 1-methyladenine (m 1 A), 3-methylcytidine (m 3 C), 5-methylcytidine (m 5 C), and 1-methylinosine (m 1 I) (Figure ). Many of these modifications and their corresponding enzymes are conserved in Eukarya, Bacteria, and Archaea. ,− …”