Zhang et al reported in Science (review, paper - subscription required) how two almost identical protein sequences can have different translational modifications. In this case, β-actin and γ-actin are 98% identical, the differences are marginal and don’t explain why one protein is modified with arginine and the other is not.
The difference is actually quite subtle - there is one amino acid in the protein sequence that is lysine in both proteins, but the codons in the RNA are different. That difference is enough to change the relative translation speed of β-actin so that it rapidly folds and gets arginylated but not degraded as happens in the slower translation of γ-actin. In the end, this affects the relative lifetime of each protein in the cell, leading to differential functions.
That’s so cool.
It seems like every so often, things we view as well understood turn out to have another layer of subtlety built in. For example, differential codon usage is usually considered a synonymous change, nothing momentous. Sure, there’s been studies of codon usage relative to the abundance of corresponding tRNAs and how that might be used to modulate abundance of a protein (a quick Google search revealed some interesting codon-usage papers). But I think this case is novel, differential codon usage actually affecting the post-translational modification of a protein simply by tweaking the speed of translation.
How might we create a codon usage table that takes into account tRNA abundance, contribution to translational speed of different codons, and speed of post-translational processes to be able to model and predict things like the differences between the functions of β-actin and γ-actin.
Also, how prevalent is this subtle effect on post-translational modification and how susceptible is it to breaking and causing trouble in a cell?
image from Science review (found via Google images, mind you)