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Simulations reveal how ribosome crowding alters mRNA structure and dynamics, with significant implications for translation efficiency.
The spatial architecture and mechanical rigidity of polysomes are crucial determinants of translational efficiency and mRNA stability. In this study, we investigate the conformational statistics of an mRNA backbone decorated with high-density ribosomes at varying densities using large-scale, extensive molecular dynamics simulations based on the Kremer-Grest bead-spring model. To address the extreme spatial asymmetry between mRNA monomers and ribosomes, we used an efficient tree-based neighbor list algorithm, enabling the analysis of mRNA chains up to N = 4969. Our results demonstrate that the excluded volume of massive ribosomes induces a significant and robust expansion of the scaling exponent ν from 0.59 to ∼0.7. In the conformation of mRNA, this shift translates to a self-induced dimensional reduction from a three-dimensional random coil toward a stretched, quasi-two-dimensional architecture at biologically relevant scales. Such a transition is further evidenced by a periodic "regain" of the bond-bond correlation function C(n) at ribosome attachment sites, indicating a geometric alignment absent in standard homopolymers. These findings reveal that the geometric crowding of ribosomes itself provides a robust physical prerequisite for the formation of higher-order polysome architectures, bridging the gap between polymer physics and structural properties of mRNA during translation.
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Kobayashi et al. (2026) studied this question.
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