A quantitative comparison of sRNA-based and protein-based gene regulation

Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (i...

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate...

Single-cell studies often show significant phenotypic variability due to the stochastic nature of intra-cellular biochemical reactions. When the numbers of molecules, e.g., transcription factors and regulatory enzymes, are in low abundance, fluctuations in biochemical activities become significant and such "noise" can propagate through regulatory cascades in terms of biochemical reaction networks. Here we develop an intuitive, yet fully quantitative method for analyzing how n...

Eukaryotic transcription generally occurs in bursts of activity lasting minutes to hours; however, state-of-the-art measurements have revealed that many of the molecular processes that underlie bursting, such as transcription factor binding to DNA, unfold on timescales of seconds. This temporal disconnect lies at the heart of a broader challenge in physical biology of predicting transcriptional outcomes and cellular decision-making from the dynamics of underlying molecular pr...

Bursting cells lead to ambient RNA that contaminates sequencing data. This process is especially problematic in perturbation experiments where transcription factors are implanted into cells to determine their effects. The presence of contaminants makes it difficult to determine whether a factor is truly expressed in the cell. This paper studies the properties of contaminant noise from an analytical perspective, showing that the cell bursting process constrains the form of the...

Living cells are continually exposed to environmental signals that vary in time. These signals are detected and processed by biochemical networks, which are often highly stochastic. To understand how cells cope with a fluctuating environment, we therefore have to understand how reliably biochemical networks can transmit time-varying signals. To this end, we must understand both the noise characteristics and the amplification properties of networks. In this manuscript, we use ...

Mathematical models of gene regulatory networks are widely used to study cell fate changes and transcriptional regulation. When designing such models, it is important to accurately account for sources of stochasticity. However, doing so can be computationally expensive and analytically untractable, posing limits on the extent of our explorations and on parameter inference. Here, we explore this challenge using the example of a simple auto-negative feedback motif, in which we ...

Biomolecular condensates have been shown to play a fundamental role in localizing biochemistry in a cell. RNA is a common constituent of condensates, and can determine their biophysical properties. Functions of biomolecular condensates are varied including activating, inhibiting, and localizing reactions. Recent theoretical work has shown that the phase separation of proteins into droplets can diminish cell to cell variability in protein abundance. However, the extent to whic...

Gene expression is a central process to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges among traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided pro...

The activation/repression of a given gene is typically regulated by multiple transcription factors (TFs) that bind at the gene regulatory region and recruit RNA polymerase (RNAP). The interactions between the promoter region and TFs and between different TFs specify the dynamic responses of the gene under different physiological conditions. By choosing specific regulatory interactions with up to three transcription factors, we designed several functional motifs, each of which...