Stop codon readthrough lessons from the tRNA anti-codon stem.

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If you imagine a gene as a sentence starting with a capital letter and ending with a period, and a genome as a book telling an entire story, it has recently been shown that specific organisms exist where extra periods infiltrated their sentences. As a result, readers (in this case ribosomes) are confused as to where these sentences really end and the story becomes disjointed. We have discovered a molecular mechanism that these organisms developed to allow the reader/ribosomes to go through their sentences as if there were no extra periods. The sentences are so specifically encrypted that readers/ribosomes of no other organisms but those very few can decipher the story in a proper way. The trick is in the nature and length of the anti-codon stem of readthrough-inducing tRNAs and mutant release factors. We have also seen these tricks to be employed in programmed stop codon readthrough in all organisms. Here, in the three-party collaboration, we will subject these critical players to an in-depth analysis and attempt to solve the structure of an 80S ribosome reading through a stop codon.