Disease Models & Mechanisms (May 2017)

RNA metabolism in neurodegenerative disease

  • Elaine Y. Liu,
  • Christopher P. Cali,
  • Edward B. Lee

DOI
https://doi.org/10.1242/dmm.028613
Journal volume & issue
Vol. 10, no. 5
pp. 509 – 518

Abstract

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Aging-related neurodegenerative diseases are progressive and fatal neurological diseases that are characterized by irreversible neuron loss and gliosis. With a growing population of aging individuals, there is a pressing need to better understand the basic biology underlying these diseases. Although diverse disease mechanisms have been implicated in neurodegeneration, a common theme of altered RNA processing has emerged as a unifying contributing factor to neurodegenerative disease. RNA processing includes a series of distinct processes, including RNA splicing, transport and stability, as well as the biogenesis of non-coding RNAs. Here, we highlight how some of these mechanisms are altered in neurodegenerative disease, including the mislocalization of RNA-binding proteins and their sequestration induced by microsatellite repeats, microRNA biogenesis alterations and defective tRNA biogenesis, as well as changes to long-intergenic non-coding RNAs. We also highlight potential therapeutic interventions for each of these mechanisms.

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