Exploring in silico transcriptional and post-transcriptional gene regulatory networks in the Corynebacterium genus

Abstract

Transcriptional and post-transcriptional regulation of gene expression are considered key regulatory steps in bacteria. Regulatory molecules such as transcription factors (TF), sigma-factors and small RNAs (sRNAs) modulate gene expression, allowing bacteria to survive and adapt to constantly changing and challenging environments. These molecules and their role in gene expression have been widely explored in model bacteria such as Escherichia coli and Bacillus subtilis. However, our understanding regarding the regulatory landscape of the Corynebacterium genus is still very limited despite its biotechnological, medical and veterinary importance. Here, we expand the transcriptional and post-transcriptional knowledge of the Corynebacterium genus. This thesis manuscript is divided into two chapters and presents three articles. In our first research article, we explore the regulation by TFs and sigma-factors in the seventh version of CoryneRegNet, the reference database for corynebacterial regulatory interactions since 2006. We predicted transcriptional regulatory interactions for 224 corynebacterial organisms, increasing by twenty times the quantity of corynebacterial organisms with known transcriptional Gene Regulatory Networks (GRNs) and assigning statistical significance values to the predicted regulatory interactions. Subsequently, we present a review article, in which, we collect, summarize and organize the knowledge regarding sRNAs and their mechanisms of action in this genus, highlighting sRNAs involved in glucose uptake, plasmid copy-number control and glutamate production. In our third research article, we expand corynebacterial post-transcriptional regulatory knowledge by enriching the GRN of six corynebacterial organisms with sRNA-driven regulatory interactions and suggest sRNAs, TF and sigma-factors jointly orchestrate gene expression regulation in this genus. In brief, this thesis presents the largest GRN database for the Corynebacterium genus, unraveling TF-, sigma- and sRNA-driven regulatory interactions. It represents a step towards the understanding of the regulatory mechanisms of the Corynebacterium genus by both presenting potential regulatory interactions and suggesting targets for further experimental investigation.