Effect of DNA replication on mRNA noise


Gene expression noise affects a cell’s biological state and contributes to such phenomena as phenotype switching and cell fate determination. J. Peterson and J. Cole of the Luthey-Schulten laboratory collaborated with J. Fei and the Ha laboratory to examine the effects of DNA replication on gene expression (mRNA) noise.  By examining chromosome replication---which is tightly controlled and thus exhibits little noise---they showed that variability in mRNA levels across a population is greatly affected by mRNA dynamics.  Applying computational methods they found that the noise is greatly affected by the transient relaxation of the mRNA from a low- to a high-copy steady state after a gene replication event.  Examining the many factors associated with gene expression and cell growth, they identified gene location, mRNA degradation rate, and cell doubling time as the main factors contributing to the observed noise. They derived analytical theories for the effect of chromosome replication on both constitutively expressed and regulated genes for use in analyzing and interpreting experimental measurements. As a demonstration, they applied the theory to fit the kinetics of transcription, degradation and regulation of the ptsG gene, which codes for the glucose phosohptransferase enzyme. Overall, their results demonstrate that it is essential to account for gene replication when modelling gene expression or when interpreting experimental results.

Read more at Peterson, J.R. (2015) PNAS 112(52):15886-15891‚Äč