Aging--RNA in development and disease

Abstract

Given that RNA is involved in virtually all biological processes, it is perhaps not surprising that several RNA-binding proteins are associated with aging and with different age-related disorders. Other articles in this volume will discuss some specific examples of diseases where RNA plays a role that are also associated with aging, such as cancer and inflammation, so here I will discuss some general aspects of how RNA changes with the aging process. I will also discuss some specific examples of RNA-binding proteins that are associated with age-dependent neurological diseases as these provide an interesting framework to examine how lifetime mutations might lead to a late onset disease, although the answers to these questions are still not well understood.

Figure 1

RNA metabolism genes associated with age-related neurodegenerative conditions. Inherited neurodegenerative diseases can be associated with mutations in genes encoding several RNA binding proteins, including TDP43 and FUS (associated with adult onset amyotrophic lateral sclerosis), SMN1 and GLE1 (associated with juvenile onset motor neuron diseases and DJ-1 (also known as PARK7, associated with recessive parkinsonism). Domains and individual regions of the proteins are indicated below the ideograms for each protein, which are presented at the same scale. Selected examples of allelic variants found in each disease are shown above each protein; in some cases there are also known duplication or insertion alleles. NLS, nuclear localization sequence; RRM, RNA recognition motif; NES, nuclear export sequence; NLR, nuclear localization region.