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

We study the response of an autoregulated gene to a range of concentrations of signal molecules. We show that transcriptional leakage and noise due to translational bursting have the opposite effects. In a positively autoregulated gene, increasing the noise converts the response from graded to binary, while increasing the leakage converts the response from binary to graded. Our findings support the hypothesis that, being a common phenomenon, leaky expression may be a relative...

Transcriptional regulation by transcription factors and post-transcriptional regulation by microRNAs constitute two major modes of regulation of gene expression. While gene expression motifs incorporating solely transcriptional regulation are well investigated, the dynamics of motifs with dual strategies of regulation, i.e., both transcriptional and post-transcriptional regulation, have not been studied as extensively. In this paper, we probe the dynamics of a four-gene motif...

It has recently been suggested that the competition for a finite pool of microRNAs (miRNA) gives rise to effective interactions among their common targets (competing endogenous RNAs or ceRNAs) that could prove to be crucial for post-transcriptional regulation (PTR). We have studied a minimal model of PTR where the emergence and the nature of such interactions can be characterized in detail at steady state. Sensitivity analysis shows that binding free energies and repression m...

Recent studies reported complex post-transcriptional interplay among targets of a common pool of microRNAs, a class of small non-coding downregulators of gene expression. Behaving as microRNA-sponges, distinct RNA species may compete for binding to microRNAs and coregulate each other in a dose-dependent manner. Although previous studies in cell populations showed competition in vitro, the detailed dynamical aspects of this process, most importantly in physiological conditions...

In this research, we study biological networks at different scales: a gene autoregulatory network at the single-cell level and the gut microbiota at the population level. Proteins are the main actors in cells, they are the building blocks, act as enzymes and antibodies. The production of proteins is mediated by transcription factors. In some cases, a protein acts as its own transcription factor, this is called autoregulation. It is known that autorepression speeds up the re...

In biochemical signaling, information is often encoded in oscillatory signals. However, the advantages of such a coding strategy over an amplitude encoding scheme of constant signals remain unclear. Here we study the dynamics of a simple model gene promoter in response to oscillating and constant transcription factor signals. We find that in biologically-relevant parameter regimes an oscillating input can produce a more constant protein level than a constant input. Our result...

Gene expression is a noisy process and several mechanisms, both transcriptional and posttranscriptional, can stabilize protein levels in cells. Much work has focused on the role of miRNAs, showing in particular that miRNA-mediated regulation can buffer expression noise for lowly expressed genes. Here, using in silico simulations and mathematical modeling, we demonstrate that miRNAs can exert a much broader influence on protein levels by orchestrating competition-induced cross...

Modelling gene regulatory networks not only requires a thorough understanding of the biological system depicted but also the ability to accurately represent this system from a mathematical perspective. Throughout this chapter, we aim to familiarise the reader with the biological processes and molecular factors at play in the process of gene expression regulation.We first describe the different interactions controlling each step of the expression process, from transcription to...

When small RNAs are loaded onto Argonaute proteins they can form the RNA-induced silencing complexes (RISCs), which mediate RNA interference. RISC-formation is dependent on a shared pool of Argonaute proteins and RISC loading factors, and is thus susceptible to competition among small RNAs for loading. We present a mathematical model that aims to understand how small RNA competition for the PTR resources affects target gene repression. We discuss that small RNA activity is li...

Genes and proteins regulate cellular functions through complex circuits of biochemical reactions. Fluctuations in the components of these regulatory networks result in noise that invariably corrupts the signal, possibly compromising function. Here, we create a practical formalism based on ideas introduced by Wiener and Kolmogorov (WK) for filtering noise in engineered communications systems to quantitatively assess the extent to which noise can be controlled in biological pro...