Figure 1.

Possible molecular consequences of CCTG nucleotide repeat expansion in the CNBP gene. Loss of function: expansion of the repeats form dsDNA secondary structures that can elicit transcriptional gene silencing, resulting in partial or complete loss of the native protein encoded by the CNBP gene. Transcribed repeated RNAs can also fold into complex structures that are sequestered into the nucleus, resulting in haploinsufficiency. RNA toxicity: transcribed CCUG repeated RNAs aberrantly interact with and sequester RNA-binding proteins, forming toxic RNA foci. Protein toxicity: non-coding RNA repeats, lacking the canonical AUG translation initiation codon, undergo non-canonical repeat-associated non-AUG (RAN) translation, thus producing LPAC (sense) and QAGR (antisense) toxic tetrapeptides. Created with BioRender.com.