Non-coding RNAs in homeostasis, disease and stress responses: an evolutionary perspective.

Cells and organisms are subject to challenges and perturbations in their environment and physiology in all stages of life. The molecular response to such changes, including insulting conditions such as pathogen infections, involves coordinated modulation of gene expression programmes and has not only homeostatic but also ecological and evolutionary importance. Although attention has been primarily focused on signalling pathways and protein networks, non-coding RNAs (ncRNAs), which comprise a significant output of the genomes of prokaryotes and especially eukaryotes, are increasingly implicated in the molecular mechanisms of these responses. Long and short ncRNAs not only regulate development and cell physiology, they are also involved in disease states, including cancers, in host-pathogen interactions, and in a variety of stress responses. Indeed, regulatory RNAs are part of genetically encoded response networks and also underpin epigenetic processes, which are emerging as key mechanisms of adaptation and transgenerational inheritance. Here we present the growing evidence that ncRNAs are intrinsically involved in cellular and organismal adaptation processes, in both robustness and protection to stresses, as well as in mechanisms generating evolutionary change.