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RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic lateral sclerosis

Ho Yin Edwin Chan1

  • 1Laboratory of Drosophila Research, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong Hong Kong, China ; Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong Hong Kong, China.

Frontiers in Cellular Neuroscience
|January 8, 2015
PubMed

Insights

RNA toxicity pathways contribute to human diseases. This review details common RNA toxicity mechanisms, including epigenetic silencing and repeat expansion disorders like polyglutamine diseases.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Gene transcription generates diverse ribonucleic acid (RNA) species with critical cellular functions.
  • Emerging research highlights RNA-mediated toxicity pathways in various human pathologies.
  • Understanding these pathways is crucial for disease mechanism elucidation.

Purpose of the Study:

  • To review and describe common RNA toxicity pathways.
  • To emphasize RNA toxicity mechanisms involving nucleotide repeat expansion.
  • To connect these mechanisms to specific human disorders.

Main Methods:

  • Literature review of RNA toxicity pathways.
  • Categorization of common RNA toxicity mechanisms.
  • Focus on nucleotide repeat expansion-associated toxicity.

Main Results:

  • Identified key RNA toxicity pathways: epigenetic gene silencing, nucleolar stress, nucleocytoplasmic transport, bi-directional gene transcription, repeat-associated non-ATG translation, RNA foci formation, and cellular protein sequestration.
  • Highlighted mechanisms involving nucleotide repeat expansion.
  • Linked these mechanisms to polyglutamine disorders and frontotemporal lobar degeneration-amyotrophic lateral sclerosis.

Conclusions:

  • RNA toxicity pathways represent a significant pathogenic mechanism in human diseases.
  • Nucleotide repeat expansions are a critical driver of RNA toxicity in specific neurological disorders.
  • Further research into RNA toxicity is essential for therapeutic development.
Keywords:
C9orf72Drosophila modelsnucleolinpolyglutamine diseaserepeat expansion-associated non-ATG translation

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