The role of modifications in codon discrimination by tRNALysUUU

Abstract

The natural modification of specific nucleosides in many tRNAs is essential during decoding of mRNA by the ribosome. For example, tRNA^Lys_UUU requires the modification N6-threonylcarbamoyladenosine at position 37 (t⁶A37), adjacent and 3′ to the anticodon, to bind AAA in the A site of the ribosomal 30S subunit. Moreover, it can only bind both AAA and AAG lysine codons when doubly modified with t⁶A37 and either 5-methylaminomethyluridine or 2-thiouridine at the wobble position (mnm⁵U34 or s²U34). Here we report crystal structures of modified tRNA anticodon stem-loops bound to the 30S ribosomal subunit with lysine codons in the A site. These structures allow the rationalization of how modifications in the anticodon loop enable decoding of both lysine codons AAA and AAG.