Dysregulation of long non-coding RNAs and their mechanisms in Huntington's disease

J Neurosci Res. 2021 Sep;99(9):2074-2090. doi: 10.1002/jnr.24825. Epub 2021 May 24.

Abstract

Extensive alterations in gene regulatory networks are a typical characteristic of Huntington's disease (HD); these include alterations in protein-coding genes and poorly understood non-coding RNAs (ncRNAs), which are associated with pathology caused by mutant huntingtin. Long non-coding RNAs (lncRNAs) are an important class of ncRNAs involved in a variety of biological functions, including transcriptional regulation and post-transcriptional modification of many targets, and likely contributed to the pathogenesis of HD. While a number of changes in lncRNAs expression have been observed in HD, little is currently known about their functions. Here, we discuss their possible mechanisms and molecular functions, with a particular focus on their roles in transcriptional regulation. These findings give us a better insight into HD pathogenesis and may provide new targets for the treatment of this neurodegenerative disease.

Keywords: mHTT; Huntington's disease; RNA; lncRNA; polyQ.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Gene Regulatory Networks / physiology*
  • Humans
  • Huntingtin Protein / genetics
  • Huntingtin Protein / metabolism*
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • HTT protein, human
  • Huntingtin Protein
  • RNA, Long Noncoding