Transcription factors involved in dauer formation under pathogenesis identified by analysis of knowledge-based networks.
Keywords: trasngenerational, C. elegans, miRNAs, networks.
Abstract
The entry into dauer of C. elegans is a widely demonstrated mechanism that is directly related to various environmental conditions such as: high population density, high temperatures, starvation or food with pathogens of medium virulence such as Salmonella Typhimurium (MST1) and Pseudomonas aeruginosa (PAO1). In our research, we wanted to demonstrate in vivo, which are the molecules involved in the formation of dauer by pathogens and who are the regulators of these molecules?. To answer this question, we carried out the transcriptomic analysis of small RNAs differentially expressed in worms fed with MST1 and PAO1, finding that mir-243-3p and mir-51-5p act as regulators of a plethora of genes and are indispensable for the formation of dauer for pathogenesis; these results in conjunction with experimentally validated data available on the interaction of transcription factors with mir-243-3p and mir-51-5p or failing that, predictions of these interactions, and the differential expression analysis of genes from worms fed with PAO1, they have allowed building a regulatory network of genes and discover transcription factors (TF) involved in the formation of dauer in response to pathogens and validate their participation in this process in vivo. The Analysis of regulatory networks formed by these miRNAs and intestinal transcription factors, differentially expressed under pathogenesis, shows that both miRNAs are part of the same regulatory circuit of aly-2, nhr-28, ama-1, crh-2, daf-16, elt- 3, fos-1, jun-1, lsy-1, mdl-1, mep-1, nhr-23, pha-1, pqm-1, snpc-4, unc-130, unc-62, and ztf-7. Of all these TF, until now we have discovered that aly-2, nhr-28, pqm-1, alr-1 and crh-2 do not form dauer in pathogens suggesting that they are directly related to the dauer process by pathogenesis being also regulators of mir-243-3p and mir-51-5p.
Más información
| Fecha de publicación: | 2019 |
| Idioma: | Ingles |
| Financiamiento/Sponsor: | 1) Center for Genomics and Bioinformatics, Universidad Mayor, Chile. 2) Centro Interdiciplinario de Neurociencia de Valparaiso (CINV). |