Neuronal Transcriptome from C9orf72 Repeat Expanded Human Tissue is Associated with Loss of C9orf72 Function.

ABSTRACT: A hexanucleotide G₄C₂ repeat expansion in C9orf72 is the most common genetic cause of familial and sporadic cases of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The mutation is associated with a reduction of C9orf72 protein and accumulation of toxic RNA and dipeptide repeat aggregates. The accumulation of toxic RNA has been proposed to sequester RNA binding proteins thereby altering RNA processing, consistent with previous transcriptome studies that have shown that the C9orf72 repeat expansion is linked to abundant splicing alterations and transcriptome changes. Here, we used a subcellular fractionation method and FACS to enrich for neuronal nuclei from C9orf72 repeat expanded post-mortem human ALS/FTD brains,

SUBMITTER: Liu EY 

PROVIDER: S-EPMC7470232 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature