Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions

Neuron. 2019 Apr 17;102(2):294-320. doi: 10.1016/j.neuron.2019.03.014.


RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA splicing, transport, and stability. Disruption of RNA binding proteins and widespread RNA processing defects are increasingly recognized as critical determinants of neurological diseases. Here, we describe distinct mechanisms by which the homeostasis of RNA binding proteins is compromised in neurological disorders through their reduced expression level, increased propensity to aggregate or sequestration by abnormal RNAs. These mechanisms all converge toward altered neuronal function highlighting the susceptibility of neurons to deleterious changes in RNA expression and the central role of RNA binding proteins in preserving neuronal integrity. Emerging therapeutic approaches to mitigate or reverse alterations of RNA binding proteins in neurological diseases are discussed.

Keywords: ALS; FMRP; RNA binding protein; Repeat expansion; SMA; SMN; TDP-43; autism; dementia; hnRNP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy
  • CRISPR-Cas Systems
  • Genetic Therapy
  • Genetic Vectors
  • Homeostasis
  • Humans
  • Molecular Targeted Therapy
  • Nervous System Diseases / genetics
  • Nervous System Diseases / metabolism*
  • Nervous System Diseases / therapy
  • Oligoribonucleotides, Antisense / therapeutic use
  • Paraneoplastic Syndromes, Nervous System / genetics
  • Paraneoplastic Syndromes, Nervous System / metabolism
  • Paraneoplastic Syndromes, Nervous System / therapy
  • RNA / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA Splicing
  • RNA Stability
  • RNA Transport
  • RNA-Binding Proteins / metabolism*


  • Oligoribonucleotides, Antisense
  • RNA-Binding Proteins
  • RNA