Connecting tRNA Charging and Decoding through the Axis of Nucleotide Modifications at Position 37

Charging and decoding of tRNA are two steps in an elongation cycle of protein synthesis that embody the essence of the genetic code. In this embodiment, the amino acid charged to the 3'-end of a tRNA is delivered to the corresponding codon via the base pairing interaction between the anticodon of the tRNA and the codon in the ribosome decoding site. Previous work has shown that the nucleotide base at position 37 on the 3'-side of the anticodon can connect charging with decoding in one elongation cycle, providing an axis to coordinate these two steps in the making of a new peptide bond. However, as much of the previous work used tRNA transcripts as substrates, lacking any post-transcriptional modification, the role of the post-transcriptional modification at position 37 in this axis has remained unknown. Here we summarize recent work that has uncovered the modifications at position 37 that are important for both charging and decoding. We find that m¹G37 and t⁶A37 are two such modifications. This review serves as a template for further discovery of tRNA modifications at position 37 that connect charging with decoding to provide the basis for better understanding of tRNA biology in human health and disease.