[Regulatory mechanisms of repeat-associated non-AUG translation: unveiling a novel molecular pathomechanism in repeat expansion diseases].

The expansion of genomic repeat sequences can cause more than 50 hereditary neuromuscular diseases, collectively referred to as repeat expansion diseases. In noncoding repeat expansion diseases caused by the expanded repeat sequences in the untranslated regions, repeat RNAs transcribed from the mutant genes can undergo repeat-associated non-AUG (RAN) translation despite lacking canonical AUG initiation codons, leading to the production of toxic repeat polypeptides that contribute to neurodegeneration. RAN translation has emerged as a promising therapeutic target for noncoding repeat expansion diseases; however, its regulatory mechanisms remain unclear. In this review, the characteristics of RAN translation and its roles in neuromuscular pathogenesis are overviewed. In addition, our research efforts for elucidating the regulatory mechanisms of RAN translation using Drosophila disease models are introduced.