MicroRNA group disorganization in aging

Abstract

Among non-coding RNAs, microRNAs may be one of the best known subgroups, due to their unique function of negatively controlling gene expression, by either degrading target messages or binding to their 3'-untranslated region to inhibit translation. Thus gene expression can be repressed through post-transcriptional regulation, implemented as a 'dimmer switch', in contrast to the all-or-none mode of suppression. Work from our laboratory and others shows that during aging, dysregulated expression of microRNAs generally occurs in groups, suggesting that their actions may be functionally coordinated as a 'pack' by common transcriptional regulators; the accumulation of these 'pack' disorganizations may be the underlying culprit contributing to the pathoetiology of many age-dependent disease states. The fact that many microRNAs are coordinated in their expression, due to either the close proximity of their genomic locations or sharing the same transcriptional regulation, suggests that future strategies for correcting age-dependent microRNA disorganization may need to involve a system biology, rather than a reductionist, approach. Therefore, understanding age-dependent changes of microRNA expression in 'packs' may open an entirely new frontier, i.e. how particular groups of non-coding RNAs, functioning together, contribute to mechanisms regulating aging and longevity.