A Bioinformatics Approach to Explore MicroRNAs as Tools to Bridge Pathways Between Plants and Animals. Is DNA Damage Response (DDR) a Potential Target Process?

MicroRNAs, highly-conserved small RNAs, act as key regulators of many biological functions in both plants and animals by post-transcriptionally regulating gene expression through interactions with their target mRNAs. The microRNA research is a dynamic field, in which new and unconventional aspects are emerging alongside well-established roles in development and stress adaptation. A recent hypothesis states that miRNAs can be transferred from one species to another and potentially target genes across distant species. Here, we propose to look into the trans-kingdom potential of miRNAs as a tool to bridge conserved pathways between plant and human cells. To this aim, a novel multi-faceted bioinformatic analysis pipeline was developed, enabling the investigation of common biological processes and genes targeted in plant and human transcriptome by a set of publicly available Medicago truncatula miRNAs. Multiple datasets, including miRNA, gene, transcript and protein sequences, expression profiles and genetic interactions, were used. Three different strategies were employed, namely a network-based pipeline, an alignment-based pipeline, and a M. truncatula network reconstruction approach, to study functional modules and to evaluate gene/protein similarities among miRNA targets. The results were compared in order to find common features, e.g., microRNAs targeting similar processes. Biological processes like exocytosis and response to viruses were common denominators in the investigated species. Since the involvement of miRNAs in the regulation of DNA damage response (DDR)-associated pathways is barely explored, especially in the plant kingdom, a special attention is given to this aspect. Hereby, miRNAs predicted to target genes involved in DNA repair, recombination and replication, chromatin remodeling, cell cycle and cell death were identified in both plants and humans, paving the way for future interdisciplinary advancements.