Coupled Transcriptional and Translational Bursting Shapes Gene Expression Noise

Noise in protein levels, arising from stochastic gene expression, is a key determinant of cellular heterogeneity and adaptive responses. Transcriptional bursting has been studied extensively, but recent findings indicate that mRNA folding–unfolding dynamics can also generate bursts at the translational stage. In this case, individual mRNAs switch between active and inactive states, with protein synthesis restricted to the active state. The combined impact of transcriptional and translational bursts on protein noise has not been systematically analyzed. Here we construct a stochastic model of gene expression that incorporates both mechanisms. Using generating function techniques, we obtain analytical expressions for average protein levels and noise. Results show that translational bursts contribute strongly to overall noise, while transcriptional bursts amplify this contribution. We further demonstrate that translation efficiency, defined as protein output per transcript, increases gene expression noise at fixed protein abundance. These findings highlight the necessity of tuning transcriptional and translational kinetics together to control protein noise, providing a unified framework for understanding noise regulation in gene expression.