Evolution of microRNA (miRNA) Structure and Function in Plants and Animals: Relevance to Aging and Disease.

Abstract

Our concepts of the structure and function of sncRNA, including miRNA and vsRNA and their regulatory mechanisms in development and aging, and how they fit into the fascinating realm of dysfunctional RNA metabolism in diseases of plants and animals, and more specifically human neurological diseases such as AD, continues to evolve. Similarities in the molecular-genetics of miRNA and viroid generation, structure and function suggest that some very basal and conserved mechanisms of disease processes have been preserved across the evolution of multiple and diverse plant and animal species. Indeed, pathogenically up-regulated miRNAs and sncRNAs can be considered as an ancient, epigenetic system used to down-regulate specific mRNAs and their expression, and this elegant regulatory system has been maintained across a plant and animal species divergence that occurred some 1.5 billion years ago [13,14,30,31,69]. Significantly up-regulated miRNAs in neurodegenerative disorders such as AD may help explain the large number of brain gene mRNAs, essential for homeostatic brain activity, that are observed to be progressively down-regulated in AD susceptible anatomical regions as AD advances [62,70,74–77]. In the case of AD, and perhaps other progressive age-related neurological diseases, miRNA- and/or anti-miRNA-directed therapeutics represent an obvious choice for future pharmacological treatment strategies, and these would enable the diseased CNS to regain more normalized and homeostatic gene expression functions.