The Role of MicroRNAs in Spinocerebellar Ataxia Type 3

J Mol Biol. 2019 Apr 19;431(9):1729-1742. doi: 10.1016/j.jmb.2019.01.019. Epub 2019 Jan 18.


More than 90% of the human genome are transcribed as non-coding RNAs. While it is still under debate if all these non-coding transcripts are functional, there is emerging evidence that RNA has several important functions in addition to coding for proteins. For example, microRNAs (miRNAs) are important regulatory RNAs that control gene expression in various biological processes and human diseases. In spinocerebellar ataxia type 3 (SCA3), a devastating neurodegenerative disease, miRNAs are involved in the disease process at different levels, including the deregulation of components of the general miRNA biogenesis machinery, as well as in the cell type-specific control of the expression of the SCA3 disease protein and other SCA3 disease-relevant proteins. However, it remains difficult to predict whether these changes are a cause or a consequence of the neurodegenerative process in SCA3. Further studies using standardized procedures for the analysis of miRNA expression and larger sample numbers are required to enhance our understanding of the miRNA-mediated processes involved in SCA3 disease and may enable the development of miRNA-based therapeutics. In this review, we summarize the findings of independent studies highlighting both the disease-related and cytoprotective roles of miRNAs that have been implicated so far in the disease process of SCA3.

Keywords: RNA-mediated toxicity; ataxin-3; cell type-specific expression; non-coding RNA; polyglutamine disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Ataxin-3 / genetics*
  • Ataxin-3 / metabolism
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Cell Line
  • Disease Models, Animal
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation
  • Humans
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Machado-Joseph Disease / genetics*
  • Machado-Joseph Disease / metabolism
  • Machado-Joseph Disease / pathology
  • Machado-Joseph Disease / therapy
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy / methods
  • Neurons / metabolism*
  • Neurons / pathology
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction


  • Biomarkers
  • MicroRNAs
  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3