Post-transcriptional regulation of noise in protein distributions during gene expression

Regulation of intrinsic noise in gene expression is essential for many cellular functions. Correspondingly, there is considerable interest in understanding how different molecular mechanisms of gene expression impact variations in protein levels across a population of cells. In this work, we analyze a stochastic model of bursty gene expression which considers general waiting-time distributions governing arrival and decay of proteins. By mapping the system to models analyzed i...

We derive exact solutions of simplified models for the temporal evolution of the protein concentration within a cell population arbitrarily far from the stationary state. We show that monitoring the dynamics can assist in modeling and understanding the nature of the noise and its role in gene expression and protein production. We introduce a new measure, the cell turnover distribution, which can be used to probe the phase of transcription of DNA into messenger RNA.

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 ...

Gene expression is a fundamental process in a living system. The small RNAs (sRNAs) is widely observed as a global regulator in gene expression. The inherent nonlinearity in this regulatory process together with the bursty production of messenger RNA (mRNA), sRNA and protein make the exact solution for this stochastic process intractable. This is particularly the case when quantifying the protein noise level, which has great impact on multiple cellular processes. Here we prop...

Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in cell-division times generates additional intercellular variability in protein levels. Moreover, as many mRNA/protein species are expressed at low-copy numbers, errors incurred in partitioning of molecules between the mother and daughter cells are sig...

The intrinsic stochasticity of gene expression can lead to large variability in protein levels for genetically identical cells. Such variability in protein levels can arise from infrequent synthesis of mRNAs which in turn give rise to bursts of protein expression. Protein expression occurring in bursts has indeed been observed experimentally and recent studies have also found evidence for transcriptional bursting, i.e. production of mRNAs in bursts. Given that there are disti...

Stochasticity in gene expression can give rise to fluctuations in protein levels and lead to phenotypic variation across a population of genetically identical cells. Recent experiments indicate that bursting and feedback mechanisms play important roles in controlling noise in gene expression and phenotypic variation. A quantitative understanding of the impact of these factors requires analysis of the corresponding stochastic models. However, for stochastic models of gene expr...

Noise in gene expression, either due to inherent stochasticity or to varying inter- and intracellular environment, can generate significant cell-to-cell variability of protein levels in clonal populations. We present a theoretical framework, based on stochastic processes, to quantify the different sources of gene expression noise taking cell division explicitly into account. Analytical, time-dependent solutions for the noise contributions arising from the major steps involved...

This paper investigates the stochastic fluctuations of the number of copies of a given protein in a cell. This problem has already been addressed in the past and closed-form expressions of the mean and variance have been obtained for a simplified stochastic model of the gene expression. These results have been obtained under the assumption that the duration of all the protein production steps are exponentially distributed. In such a case, a Markovian approach (via Fokker-Plan...

Over the last several decades it has been increasingly recognized that stochastic processes play a central role in transcription. Though many stochastic effects have been explained, the source of transcriptional bursting (one of the most well-known sources of stochasticity) has continued to evade understanding. Recent results have pointed to mechanical feedback as the source of transcriptional bursting but a reconciliation of this perspective with preexisting views of transcr...