John A. Cole and Zaida Luthey-Schulten.
Careful accounting of extrinsic noise in protein expression reveals
correlations among its sources.
Physical Review E, 95:062418, 2017.
(PMC: PMC5669626)
COLE2017-ZLS
In order to grow and replicate, living cells must express a diverse array of
proteins, but the process by which proteins are made includes a great deal
of
inherent randomness. Understanding this randomness-whether it arises
from
the discrete stochastic nature of chemical reactivity ("intrinsic" noise), or
from
cell-to-cell variability in the concentrations of molecules involved in gene
expression, or from the timings of important cell-cycle events like DNA
replication and cell division ("extrinsic" noise)-remains a challenge. In this
article we analyze a model of gene expression that accounts for several
extrinsic sources of noise, including those associated with chromosomal
replication, cell division, and variability in the numbers of RNA polymerase,
ribonuclease E, and ribosomes. We then attempt to fit our model to a large
proteomics and transcriptomics data set and find that only through the
introduction of a few key correlations among the extrinsic noise sources
can
we accurately recapitulate the experimental data. These include significant
correlations between the rate of mRNA degradation (mediated by
ribonuclease
E) and the rates of both transcription (RNA polymerase) and translation
(ribosomes) and, strikingly, an anticorrelation between the transcription
and
the translation rates themselves.
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