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Ribosome demand links transcriptional bursts to protein expression noise

Dhar, Riddhiman1; Pal, Sampriti1; Ray, Upasana1

Published Nov 21, 2025 on Dryad. https://doi.org/10.5061/dryad.tb2rbp06x

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Abstract

The translation process modulates stochastic fluctuations in mRNA numbers and determines noise in protein expression. Studies across different organisms have revealed a positive correlation between translational efficiency and protein noise. However, the molecular basis of this correlation has remained unknown. Through stochastic modeling of translation in single mRNA molecules and empirical measurement of protein noise, we demonstrate that ribosome demand associated with high translational efficiency leads to the correlation between translational efficiency and protein noise. We also show that this correlation is present only in promoters with bursty transcription, where ribosome demand varies with stochastic fluctuations in mRNA numbers. Thus, our work shows how transcriptional bursts are translated into protein noise, which has implications for investigating noise and phenotypic heterogeneity across biological systems.