Extrinsic noise effects on ribosomal traffic during the translation process

Abstract

Any cellular process at the microscopic level is governed by both extrinsic and intrinsic noise (IN) and same is true for mRNA translation as well. Even though the effect of stochasticity via the IN is well studied for mRNA translation, same cannot be said about extrinsic noise (EN). In this article, we incorporate EN in a model of mRNA translation and carry out stochastic simulations of the same. We then evaluate various statistics related to the residence time of the ribosome and the ribosomal traffic on the mRNA and subsequent protein production. We also study the effect of slow codons and ribosome dropoff. From our simulations, we show that noise in the translation initiation rate rather than the translation termination rate acts to significantly broaden the distribution of ribosome residence times on the mRNA lattice. This EN also has an effect on ribosomal current, density and protein production. Further, the presence of slow codons acts to increase the mean residence times. However, this increase also depends on the number and position of the slow codons on the lattice. We also show that the slow codons act to mask any effect from the EN themselves. Our results, therefore, have implications towards a better understanding of the role the individual components play during the translation process.