Figure 2.
Model of RAN translation across repeats in coding and non-coding gene regions. Schematic diagram showing mutations located in intronic or exonic regions with expression of distinct RAN proteins in three frames from sense and antisense directions. For expansions in introns, sense and antisense transcripts (not shown) produce RAN proteins with different repeat motifs and distinct C-terminal regions not corresponding to any endogenous proteins. For repeat-expansion mutations located in ORFs, up to six distinct RAN proteins may be produced from sense and antisense transcripts (see upper inset for antisense RAN proteins). The RAN protein expressed in the ORF is predicted to start at or close to the repeat and contain the same C-terminal region as the protein expressed from the canonical ATG-initiated ORF. Variability of RAN proteins will occur when expressed from: sense or antisense transcripts; different repeat motifs and with variations in C-terminal sequences.