At least 92 distinct tRNA nucleotide base modifications have been found. The modifications are made post-transcriptionally by a large group of disparate enzymes located in the nucleus, cytosol, and mitochondria (reviewed in Boschi-Muller and Motorin 2013, Jackman and Alfonzo 2013, Gu et al. 2014, Helm and Alfonzo 2014, Li and Mason 2014). Modifications near the anticodon and near the 3' end affect interaction of the tRNA with ribosomes and tRNA synthetases, respectively, while modifications in other regions of the tRNA affect folding and stability of the tRNA (reviewed in Hou et al. 2015). Mutations in tRNA modification enzymes are associated with human diseases (reviewed in Sarin and Leidel 2014, Torres et al. 2014).