Repeat-associated non-AUG translation in neuromuscular diseases: mechanisms and therapeutic insights.
J Biochem
; 173(4): 273-281, 2023 Mar 31.
Article
in En
| MEDLINE
| ID: mdl-36748359
ABSTRACT
Expanded short tandem repeats cause more than 50 monogenic diseases, which are mostly neuromuscular diseases. In the non-coding repeat expansion diseases, in which the expanded repeat sequence is located outside of the coding region, the toxicity of the transcribed repeat-containing RNAs had been the focus of research. However, recent studies have revealed that repeat RNAs can be translated into repeat polypeptides, despite the lack of an AUG initiation codon, by non-canonical repeat-associated non-AUG translation (RAN translation). RAN translated repeat polypeptides have actually been confirmed in patients' tissues. Moreover, various cellular and animal disease models have demonstrated the toxicity of these peptides, suggesting the pathogenic roles of RAN translation in the repeat expansion diseases. In this review, we will outline RAN translation, from the viewpoint of its molecular mechanisms to its potential as a therapeutic target for the repeat expansion diseases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA
/
Neuromuscular Diseases
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Biochem
Year:
2023
Document type:
Article
Affiliation country:
Japón