Congrats to first author Ha An @haannguyen2 for her recent work published in PNAS on the correlation of different sequence elements in tRNAs required for accurate selection of tRNAs during decoding! @EmoryBiochem @EmoryChem @PNASNews @EmoryMedicine https://www.pnas.org/content/early/2020/06/26/2004170117

Ha An asked - how are tRNAs evolutionarily tuned to bind to the ribosome with similar affinities? Thankfully Okle Uhlenbeck’s lab performed beautiful biochemical studies that showed that the identity of specific anticodon loop nucleotides in tRNAs are correlated

to the strength of the anticodon. tRNAs containing “stronger” anticodons (more G-C pairs) require a weaker 32-38 nucleotide pairing in the anticodon loop.

This correlation allows for all tRNAs to bind to the ribosome with similar affinities regardless of their nucleotide sequences, modifications or the aminoacyl group attached.

What if this correlation is disrupted? The ribosome can’t distinguish correct from incorrect tRNAs. Whoa!

Ha An solved four different ribosome structures where she look at a wild-type tRNA bound to either correct or incorrect (near-cognate) mRNA codons and then compared these to mutant tRNAs also bound to correct or incorrect (near-cognate) mRNA codons.

Surprisingly, she found that 23S rRNA nucleotide A1913 interacts with the anticodon loop in the context of a correct wild-type tRNA-mRNA pair. When there is an incorrect codon-anticodon pair, the 32-38 interaction is more mobile and the A1913 moves away from the tRNA.

In the case of the mutant tRNAs, A1913 always engages the anticodon loop regardless of a correct or incorrect pairing signifying that these interactions bypass proofreading mechanisms. What a surprisingly result! Congrats Ha An! @haannguyen2