224 research outputs found
Stochastic modeling of regulation of gene expression by multiple small RNAs
A wealth of new research has highlighted the critical roles of small RNAs
(sRNAs) in diverse processes such as quorum sensing and cellular responses to
stress. The pathways controlling these processes often have a central motif
comprising of a master regulator protein whose expression is controlled by
multiple sRNAs. However, the regulation of stochastic gene expression of a
single target gene by multiple sRNAs is currently not well understood. To
address this issue, we analyze a stochastic model of regulation of gene
expression by multiple sRNAs. For this model, we derive exact analytic results
for the regulated protein distribution including compact expressions for its
mean and variance. The derived results provide novel insights into the roles of
multiple sRNAs in fine-tuning the noise in gene expression. In particular, we
show that, in contrast to regulation by a single sRNA, multiple sRNAs provide a
mechanism for independently controlling the mean and variance of the regulated
protein distribution
Regulation by small RNAs via coupled degradation: mean-field and variational approaches
Regulatory genes called small RNAs (sRNAs) are known to play critical roles
in cellular responses to changing environments. For several sRNAs, regulation
is effected by coupled stoichiometric degradation with messenger RNAs (mRNAs).
The nonlinearity inherent in this regulatory scheme indicates that exact
analytical solutions for the corresponding stochastic models are intractable.
Here, we present a variational approach to analyze a well-studied stochastic
model for regulation by sRNAs via coupled degradation. The proposed approach is
efficient and provides accurate estimates of mean mRNA levels as well as higher
order terms. Results from the variational ansatz are in excellent agreement
with data from stochastic simulations for a wide range of parameters, including
regions of parameter space where mean-field approaches break down. The proposed
approach can be applied to quantitatively model stochastic gene expression in
complex regulatory networks.Comment: 4 pages, 3 figure
Exact protein distributions for stochastic models of gene expression using partitioning of Poisson processes
Stochasticity in gene expression gives rise to fluctuations in protein levels
across a population of genetically identical cells. Such fluctuations can lead
to phenotypic variation in clonal populations, hence there is considerable
interest in quantifying noise in gene expression using stochastic models.
However, obtaining exact analytical results for protein distributions has been
an intractable task for all but the simplest models. Here, we invoke the
partitioning property of Poisson processes to develop a mapping that
significantly simplifies the analysis of stochastic models of gene expression.
The mapping leads to exact protein distributions using results for mRNA
distributions in models with promoter-based regulation. Using this approach, we
derive exact analytical results for steady-state and time-dependent
distributions for the basic 2-stage model of gene expression. Furthermore, we
show how the mapping leads to exact protein distributions for extensions of the
basic model that include the effects of post-transcriptional and
post-translational regulation. The approach developed in this work is widely
applicable and can contribute to a quantitative understanding of stochasticity
in gene expression and its regulation.Comment: 10 pages, 5 figure
Prediction of CsrA-regulating small RNAs in bacteria and their experimental verification in Vibrio fischeri
The role of small RNAs as critical components of global regulatory networks has been highlighted by several recent studies. An important class of such small RNAs is represented by CsrB and CsrC of Escherichia coli, which control the activity of the global regulator CsrA. Given the critical role played by CsrA in several bacterial species, an important problem is the identification of CsrA-regulating small RNAs. In this paper, we develop a computer program (CSRNA_FIND) designed to locate potential CsrA-regulating small RNAs in bacteria. Using CSRNA_FIND to search the genomes of bacteria having homologs of CsrA, we identify all the experimentally known CsrA-regulating small RNAs and also make predictions for several novel small RNAs. We have verified experimentally our predictions for two CsrA-regulating small RNAs in Vibrio fischeri. As more genomes are sequenced, CSRNA_FIND can be used to locate the corresponding small RNAs that regulate CsrA homologs. This work thus opens up several avenues of research in understanding the mode of CsrA regulation through small RNAs in bacteria
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