Hypothesis and Theory: Roles of Arginine Methylation in C9orf72-Mediated ALS and FTD

• DOI: 10.3389/fncel.2021.633668
• Publication Date: 2021-03-23T05:34:24Z
• Authors: Anna L. Gill; Alan S. Premasiri; Fernando G. Vieira
• Keywords: C9ORF72

Hexanucleotide repeat expansion (G4C2 n ) mutations in the gene C9ORF72 account for approximately 30% of familial cases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well 7% sporadic ALS. G4C2 are known to result production five species dipeptide proteins (DRPs) through non-canonical translation processes. Arginine-enriched proteins, glycine-arginine (polyGR), proline-arginine (polyPR) have been demonstrated be cytotoxic deleterious multiple experimental systems. Recently, we others implicated methylation polyGR/polyPR arginine residues disease processes related mutation-mediated neurodegeneration. We previously reported that inhibition asymmetric dimethylation (ADMe) is protective cell-based models cytotoxicity. These results consistent with idea PRMT-mediated context exposure harmful. However, it remains unclear why. Here discuss influence on diverse cellular including liquid-liquid phase separation, chromatin remodeling, transcription, RNA processing, RNA-binding protein localization, consider how may disrupt essential normal function survival.