Theodicy: irreducibly complex controls of transcription (Introduction)

by David Turell @, Thursday, September 30, 2021, 19:22 (901 days ago) @ David Turell

The latest findings:

https://www.science.org/doi/full/10.1126/science.abi7801

"Protein synthesis concludes when a ribosome encounters a stop codon in a transcript, which triggers the recruitment of highly conserved release factors to liberate the protein product. Lawson et al. used traditional biochemical methods and single-molecule fluorescence assays to track the interplay of release factors with ribosomes and reveal the molecular choreography of termination. They identified two distinct classes of effectors, small molecules and mRNA sequences, that directly inhibited the release factors and promoted stop codon readthrough. These findings may buttress ongoing efforts to treat diseases caused by premature stop codons, which cause 11% of all heritable human diseases.

"Translation termination, which liberates a nascent polypeptide from the ribosome specifically at stop codons, must occur accurately and rapidly. We established single-molecule fluorescence assays to track the dynamics of ribosomes and two requisite release factors (eRF1 and eRF3) throughout termination using an in vitro–reconstituted yeast translation system. We found that the two eukaryotic release factors bound together to recognize stop codons rapidly and elicit termination through a tightly regulated, multistep process that resembles transfer RNA selection during translation elongation. Because the release factors are conserved from yeast to humans, the molecular events that underlie yeast translation termination are likely broadly fundamental to eukaryotic protein synthesis.

***

"The fidelity of translation elongation is driven in part by kinetic proofreading, in which EF-Tu/eEF1A preferentially rejects noncognate tRNAs in two sequential steps to boost overall accuracy. Although the basis of termination fidelity is unknown, we consider kinetic proofreading a plausible model. eRF3 is essential for termination fidelity, because its inclusion boosts specificity by 2600-fold. Here, we show that eRF3 conformationally unlocks and delivers eRF1 to ribosomes and facilitates eRF1 accommodation in an eRF3 GTPase–dependent manner, thus providing eRF3 with multiple opportunities to favor genuine stop codons. Further study of termination substep kinetics at cognate and near-cognate stop codons will reveal whether proofreading governs eukaryotic termination fidelity."

Comment: From the ID folks who reviewed this article:

"Another Irreducibly Complex System
This short look at stop codons and how they trigger a coordinated series of actions in ribosomes reveals another irreducibly complex (IC) system at work. Stop codons keep us alive and healthy unless mutations, like lawbreakers, “run the red light” and violate the rules. What molecular biologists have uncovered since Darwin’s Black Box introduced the concept of irreducible complexity is not just an IC system here or there, but an IC set of IC systems at work. If one IC system defeats evolution, how much more a superset of IC systems? It’s important that people learn about the details of some of these systems to avoid being fooled by simplistic visions of cells emerging from primordial goo. Confidence in intelligent design comes when they say, “I see IC in the details.'”

I can't express it any better. God edited His system, but free-to-change-shape molecules can make uncontrollable mistakes.


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