Can a cell keep building a protein by skipping over its genetic stop signal?

Details

Translational reading gaps occur when information encoded in mRNA is left untranslated during normal protein synthesis. Previously, this phenomenon had been observed only in prokaryotes, where it can extend a protein’s reading frame by bypassing the normal stop codon. A reading frame can also be extended through stop-codon suppression mediated by a suppressor tRNA.

To determine how the reading frame is extended, the researchers sequenced rabbit beta-globin read-through protein using ion trap mass spectrometry. The abstract describes it as the only known naturally occurring read-through protein in eukaryotes.

They detected seven different proteolytic peptide fragments encoded by the same sequence spanning the UGA stop codon in rabbit beta-globin mRNA. Three of the seven peptides contained translational reading gaps of one to three amino acids, corresponding to the UGA stop-codon site and/or one or two immediately downstream codons. The authors describe this as, to their knowledge, the first reported example of reading gaps during protein synthesis in eukaryotes. They characterize the event as unique because the bypasses involve differing lengths of untranslated information.

The other four of the seven peptides contained serine, tryptophan, cysteine, and arginine decoded at UGA, indicating that these peptides arose through stop-codon suppression. Serine is donated by selenocysteine tRNA. This tRNA, like the other tRNAs, had previously been shown to suppress UGA in mammals in vitro, but not in vivo.