An Integrated Database of Small RNAs and Their Interplay With Transcriptional Gene Regulatory Networks in Corynebacteria

Abstract

Small RNAs (sRNAs) are one of the key players in the post-transcriptional regulation of bacterial gene expression. These molecules, together with transcription factors, form regulatory networks and greatly influence the bacterial regulatory landscape. Little is known concerning sRNAs and their influence on the regulatory machinery in the genus Corynebacterium, despite its medical, veterinary and biotechnological importance. Here, we expand corynebacterial regulatory knowledge by integrating sRNAs and their regulatory interactions into the transcriptional regulatory networks of six corynebacterial species, covering four human and animal pathogens, and integrate this data into the CoryneRegNet database. To this end, we predicted sRNAs to regulate 754 genes, including 206 transcription factors, in corynebacterial gene regulatory networks. Amongst them, the sRNA Cd-NCTC13129-sRNA-2 is predicted to directly regulate ydfH, which indirectly regulates 66 genes, including the global regulator glxR in C. diphtheriae. All of the sRNA-enriched regulatory networks of the genus Corynebacterium have been made publicly available in the newest release of CoryneRegNet(www.exbio.wzw.tum.de/coryneregnet/) to aid in providing valuable insights and to guide future experiments.

Keywords: CoryneRegNet; Corynebacterium; gene regulatory networks; sRNA targets; small RNAs.

FIGURE 1

Overview of the sRNA data integration workflow.

FIGURE 2

CoryneRegNet’s front-end updates in (A,B) search page and (C,D) in the network visualization. (A) The search page of CoryneRegNet’s database allows for choosing between searching for mRNA genes or sRNA genes while (B) guiding the search with gene or sRNA identifiers. (C) Direct regulations of cg0012 and (D) genes regulated by cgb_07555. In the network, green nodes represent activator proteins, red nodes represent repressor proteins, blue nodes represent dual regulators (i.e., that can activate and repress gene expression), orange nodes represent sRNAs and gray nodes represent target genes. The arrows represent the regulatory interactions and their colors represent the same roles as in the nodes.

FIGURE 3

CoryneRegNet 7.5’s sRNA details page with (A) essential information of the sRNA cgb_07555 and (B) its regulations.

FIGURE 4

C. glutamicum’s predicted sRNA-enriched regulons. (A) sdhCC and acn co-regulated by TFs and sRNAs and forming two regulatory circuits, Cg-DOR-1 and Cg-FF-1. (B) pstA being directly and indirectly regulated by TFs and sRNAs, forming the regulatory circuit Cg-FF-2. (C) marZ being regulated by 22 sRNAs. In the networks, green nodes represent activator proteins, red nodes represent repressor proteins, blue nodes represent dual regulators (i.e., that can activate and repress gene expression), orange nodes represent sRNAs and gray nodes represent target genes. The arrows represent the regulatory interactions and their colors represent the same roles as the ones in the nodes.

FIGURE 5

Genes regulated by sRNAs and regulatory proteins in C. diphtheriae NCTC 13129. In the network, green nodes represent activator proteins, red nodes represent repressor proteins, blue nodes represent dual regulators (i.e., that can activate and repress gene expression), orange nodes represent sRNAs and gray nodes represent target genes. The arrows represent the regulatory interactions and their colors represent the same roles as the ones in the nodes.

FIGURE 6

Genes regulated by sRNAs and regulatory proteins in C. jeikeium K411. In the network, green nodes represent activator proteins, red nodes represent repressor proteins, blue nodes represent dual regulators (i.e., that can activate and repress gene expression), orange nodes represent sRNAs and gray nodes represent target genes. The arrows represent the regulatory interactions and their colors represent the same roles as the ones in the nodes.

FIGURE 7

Genes regulated by sRNAs and regulatory proteins in C. pseudotuberculosis 1002B (A) and in C. ulcerans (B). In the network, green nodes represent activator proteins, red nodes represent repressor proteins, blue nodes represent dual regulators (i.e., that can activate and repress gene expression), orange nodes represent sRNAs and gray nodes represent target genes. The arrows represent the regulatory interactions and its colors represent the same roles as the ones in the nodes.