Abstract
Declining brain and neurobiological function is arguably one of the most common features of human aging. The study of conserved aging processes as well as the characterization of various neurodegenerative diseases using different genetic models such as yeast, fly, mouse, and human systems is uncovering links to non-coding RNAs. These links implicate a variety of RNA-regulatory processes, including microRNA function, paraspeckle formation, RNA–DNA hybrid regulation, nucleolar RNAs and toxic RNA clearance, amongst others. Here we highlight these connections and reveal over-arching themes or questions related to recently appreciated roles of non-coding RNA in neural function and dysfunction across lifespan.
Highlights
Neurodegenerative diseases are a group of debilitating neurological disorders typically associated with old age (Eacker et al, 2009)
Many long non-coding RNA (lncRNA) are molecularly indistinguishable from mRNAs; they are produced by Pol II and undergo 5 capping and polyadenylation (Ip and Nakagawa, 2012)
While much progress has been made in our understanding of the roles of non-coding RNA (ncRNA) in neural function, many questions still remain
Summary
Neurodegenerative diseases are a group of debilitating neurological disorders typically associated with old age (Eacker et al, 2009). Consistent with a role in neuroprotection, diminished levels of miR-29 family members have been reported in both patients or mouse models of AD, HD, and various subtypes of SCA (Lee et al, 2011; Wang et al, 2011b) The notion that these patterns may represent disease-promoting mechanisms rather than just correlational markers stems from the observation that perturbing miR-29 function is associated with compromised neuronal survival. Altered expression profiles of multiple TDP-43-regulated miRNAs is observed in serum and lymphoblast cell lines derived from ALS patients (Freischmidt et al, 2013) Taken together, these studies suggest that miRNA dysfunction downstream of disease-linked TDP-43 alterations could represent an important pathogenic mechanism in neurodegenerative disease and warrants further investigation (Figure 1). The proper genesis and function of different types of small ncRNAs is important for maintaining neural cell populations and preventing neurodegenerative disease
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