RNA metabolism in neurodegenerative disease

Dis Model Mech. 2017 May 1;10(5):509-518. doi: 10.1242/dmm.028613.


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.

Keywords: Disease; Microsatellite repeats; RNA; RNA binding proteins; lncRNA; miRNA; tRNA.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytoplasm / metabolism
  • Humans
  • MicroRNAs / genetics
  • Microsatellite Repeats
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • RNA / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA, Untranslated / genetics
  • RNA-Binding Proteins / metabolism


  • MicroRNAs
  • RNA, Untranslated
  • RNA-Binding Proteins
  • RNA