570% more mRNA start codons have been discovered – with differing expression probability!
Does this reveal another dimension in design of expression rate control?
‘Start Codons’ in DNA and RNA May Be More Numerous Than Previously Thought NIST Feb. 21, 2017
A central principle regarding translation has long held that only a small number of three-letter sequences in mRNA, known as start codons, could trigger the production of proteins. . . . “What if the results indicated that codons didn’t fit a traditional description of start or not, but instead had varying likelihoods to start translation?” . . .“We thought we knew the rules, but it turns out there’s a whole other level we need to learn about. The grammar of DNA might be even more sophisticated than we imagined. . . .“It could be that all codons could be start codons,” Hecht said. “I think it is just a matter of being able to measure them at the right level.”
Measurements of translation initiation from all 64 codons in E. coli
Ariel Hecht Jeff Glasgow Paul R. Jaschke Lukmaan A. Bawazer Matthew S. Munson Jennifer R. Cochran Drew Endy Marc Salit, Nucleic Acids Res gkx070. DOI: https://doi.org/10.1093/nar/gkx070, Published: 21 February 2017
Our understanding of translation underpins our capacity to engineer living systems. The canonical start codon (AUG) and a few near-cognates (GUG, UUG) are considered as the ‘start codons’ for translation initiation in Escherichia coli. Translation is typically not thought to initiate from the 61 remaining codons. Here, we quantified translation initiation of green fluorescent protein and nanoluciferase in E. coli from all 64 triplet codons and across a range of DNA copy number. We detected initiation of protein synthesis above measurement background for 47 codons. Translation from non-canonical start codons ranged from 0.007 to 3% relative to translation from AUG. Translation from 17 non-AUG codons exceeded the highest reported rates of non-cognate codon recognition. Translation initiation from non-canonical start codons may contribute to the synthesis of peptides in both natural and synthetic biological systems.