Downstream mRNA Secondary Structure, Not Codon Elongation Supply, Coordinates Co-Translational Protein Folding Across the Human Ribosomal Exit Tunnel
How ribosomes pace translation to assist nascent protein folding remains an open question in molecular biology. While synonymous codon selection is widely hypothesized to regulate elongation rates to facilitate domain organization, distinguishing genuine translational kinetics from baseline amino acid preferences has proven technically difficult. Here, we analyze a non-redundant cohort of 1,270…
A recent study examines the relationship between ribosome activity and protein folding in human cells. While previous research has focused on the influence of codon selection on translation speed, a new analysis reveals that mRNA secondary structure plays a crucial role in coordinating co-translational protein folding. By analyzing 1,270 high-resolution human crystal structures, researchers found that codon-supply metrics, such as the tRNA Adaptation Index and the Codon Adaptation Index, have little independent spatial coupling with downstream protein structure.
Instead, the stability of mRNA secondary structure, measured by minimum free energy, shows a consistent correlation that persists even after controlling for amino acid preferences. This subtle correlation emerges at an offset of +15 to +16 codons across various physical properties, including residue packing density. The findings suggest that downstream mRNA secondary structure stability, rather than codon elongation supply, is the key factor in coordinating protein folding during translation in human cells.
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