Computational analysis of the oscillatory behavior at the translation level induced by mRNA levels oscillations due to finite intracellular resources

In this study, based on a whole-cell model simulation of translation inS. cerevisiae, we evaluate for the first time the expected effect of mRNA levels fluctuations on translation due to the finite pool of ribosomes. We show that fluctuations of a single gene or a group of genes mRNA levels induce periodic behavior in allS. cerevisiae translation factors and aspects: the ribosomal densities and the translation rates of allS. cerevisiae mRNAs oscillate. We numerically measure the oscillation amplitudes demonstrating that fluctuations of endogenous and heterologous genes can cause a significant fluctuation of up to 50% in the steady-state translation rates of the rest of the genes. Furthermore, we demonstrate by synonymous mutations that oscillating the levels of mRNAs that experience high ribosomal occupancy (e.g. ribosomal “traffic jam”) induces the largest impact on the translation of theS. cerevisiae genome.
The results reported here should provide novel insights and principles related to the design of synthetic gene expression circuits and related to the evolutionary constraints shaping gene expression of endogenous genes.

Source: PLoS Computational Biology - April 3, 2018 Category: Biology Authors: Yoram Zarai Source Type: research