Resource competition controls the length-dependence of synaptic protein synthesis

Rubisch, P.; Raak, S. B.; Wodke, J. A. H.; Stefan, M. I.; O'Donnell, C.

doi:10.64898/2026.10.30.763010

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bioRxiv · 10.64898/2026.10.30.763010

Resource competition controls the length-dependence of synaptic protein synthesis

Rubisch, P.·Raak, S. B.·Wodke, J. A. H.·Stefan, M. I.·O'Donnell, C.

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Abstract

Synaptic plasticity is dependent on the availability of specific proteins at the synapse with distinct requirements for potentiation and depression. Specifically, experimental evidence suggests an upregulation of short proteins and a downregulation for long proteins during long-term depression (LTD). The mechanism of this length-dependent protein synthesis regulation is yet unknown. In this work, we propose an computational model of ribosomal regulation of protein synthesis than can reproduce the length-dependent shift in protein expression seen during ribosomal elevations. By analysing the model dynamics, we discover that this effect is due to a shift from initiation-restricted to elongation-restricted protein synthesis. This works offers a novel explanation for the loss of ribosomal control of protein synthesis due to saturation in pathological ribosome enriched conditions. This new theoretical model of ribosomal regulation of protein synthesis is capable of explaining length-dependent shifts in protein synthesis.

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Rubisch, P., Raak, S. B., Wodke, J. A. H., Stefan, M. I., O'Donnell, C.. 2026-11-02. Resource competition controls the length-dependence of synaptic protein synthesis. https://doi.org/10.64898/2026.10.30.763010

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