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Now not 7 but 47 mRNA start codons?!

David L. Hagen
March 1, 2017
'Junk DNA', Cell biology, Design inference, Genomics, Intelligent Design
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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

ABSTRACT
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.

Comments
From the last paragraph in the “Discussion” section of the paper referenced @1: "...encourage [...] further exploration..." That shouldn't hurt. :) Keep looking at the fish. They ain’t seen nothing yet. The best is still ahead. Dionisio
From the last paragraph in the “Discussion” section of the paper referenced @1: "... encourage reconsidering existing definitions..." That seems quite [r]evolutionary, doesn't it? :) Dionisio
From the last paragraph in the “Discussion” section of the paper referenced @1: "...would have widespread implications for [...] our fundamental understanding of translation initiation." Yes, that's part of scientific research. With every new discovery the big picture gets clearer. That's why we should look forward, with increasing anticipation, to reading future research papers about new discoveries shedding more light on the elaborate molecular and cellular choreographies orchestrated within the biological systems. Dionisio
From the last paragraph in the “Discussion” section of the paper referenced @1: "...remain undiscovered because nobody has looked for them." Well, that could happen. Sometimes certain things could be discovered while looking for something else. Serendipity? But many times if nobody has looked for certain things then it's very possible that they remain undiscovered. Perhaps a question to ask in this particular case is why nobody has looked for them? Dionisio
From the last paragraph in the "Discussion" section of the paper referenced @1: "One possibility is that..." "Another possibility is that..." Guessing or speculating, but really many times they have no idea why things happen and many times they have no idea how things happen. But that's part of the scientific research. Keep looking at the fish. We ain't seen nothing yet. :) Dionisio
"We wonder why..." Yes, that's the sense of wonder we had as children but we lost as we turned older and became absorbed in the mundane routines of the worldly existence. Glad to see they "wonder why..." again. That's encouraging. :) Scientist should humbly think with open minds. They should humbly think beyond potentially misleading preconceived paradigms. They should test everything and hold what is good. Dionisio
We wonder why so few genes have been annotated with non-canonical start codons in bacterial genomes. [it’s possible] that many naturally occurring non-canonical start codons and so-initiated proteins remain undiscovered because nobody has looked for them. The presence of frequent but very low-level expression of proteins via non-canonical start codons would have widespread implications for genome annotation, cellular engineering and our fundamental understanding of translation initiation. We encourage reconsidering existing definitions and further exploration of what is considered a start codon. 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
Dionisio

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