Pathogenic repeat-expanded C9orf72 RNA (C9orf72 repeat RNA)

Pathogenic repeat-expanded C9orf72 RNA refers to abnormally long, non-coding RNA transcripts generated from a GGGGCC (G4C2) hexanucleotide repeat expansion in the first intron of the *C9orf72* gene. These RNA species are bidirectionally transcribed and form stable, abnormal secondary structures (such as G-quadruplexes and hairpins) that result in nuclear RNA foci. The pathogenicity arises through several mechanisms: sequestration of essential RNA-binding proteins, nucleocytoplasmic transport deficits, and serving as templates for repeat-associated non-ATG (RAN) translation, producing toxic dipeptide repeat proteins. These processes collectively contribute to cell dysfunction and death in the nervous system, making this molecule a validated therapeutic target in ALS and FTD research. Therapeutics under investigation include antisense oligonucleotides and genome-editing approaches that aim to reduce levels of toxic repeat-expanded RNAs and their protein products[1][2][4][5][6].

Other names

C9orf72 hexanucleotide repeat RNAGGGGCC repeat RNAG4C2 repeat RNAC9orf72 G4C2 RNAC9ORF72 repeat expansion RNA

Antisense oligonucleotides: bind and degrade or modulate splicing of repeat-expanded C9orf72 RNA, reducing toxic gain-of-function effects[6]; CRISPR/Cas9-mediated excision: removes repeat expansion from genomic DNA to suppress both toxic RNA and dipeptide repeats[6]; RNA-targeting therapies: aim to prevent sequestration of RNA-binding proteins, formation of RNA foci, or RAN translation[1][5]