Modulation of nuclear REST by alternative splicing: a potential therapeutic target for Huntington's disease.

ABSTRACT: Huntington's disease (HD) is caused by a genetically mutated huntingtin (mHtt) protein with expanded polyQ stretch, which impairs cytosolic sequestration of the repressor element-1 silencing transcription factor (REST), resulting in excessive nuclear REST and subsequent repression of neuronal genes. We recently demonstrated that REST undergoes extensive, context-dependent alternative splicing, of which exon-3 skipping (∆E₃ )-a common event in human and nonhuman primates-causes loss of a motif critical for REST nuclear targeting. This study aimed to determine whether ∆E₃ can be targeted to reduce nuclear REST and rescue neuronal gene expression in mouse striatal-derived, mHtt-expressing STHdh^Q111/Q111 cells-a well-established cellular model of HD. We designe

SUBMITTER: Chen GL 

PROVIDER: S-EPMC5661251 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature