The repeat expansion in the human genome contributes to neurodegenerative disorders such as spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis. Transcripts with repeat expansions undergo noncanonical translation called repeat-associated non-AUG (RAN) translation. The NOP56 gene, implicated in SCA36, contains a GGCCTG repeat in its first intron. In tissues of patients with SCA36, poly (Gly-Pro) and poly (Pro-Arg) peptides, likely produced through NOP56 RAN translation in (NOP56-RAN), have been detected. However, the detailed mechanism underlying NOP56-RAN remains unclear. To address this, we used cell-free translation systems to investigate the mechanism of NOP56-RAN and identified the following features. (i) Translation occurs in all reading frames of the sense strand of NOP56 intron 1. (ii) Translation is initiated in a 5' cap-dependent manner from near-cognate start codons upstream of the GGCCUG repeat in each frame. (iii) Longer GGCCUG repeats enhance NOP56-RAN. (iv) A frameshift occurs within the GGCCUG repeat. These findings provide insights into the similarities between NOP56-RAN and other types of RAN translation.
Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.
阅读:2
作者:Hasumi Mayuka, Ito Hayato, Machida Kodai, Niwa Tatsuya, Taminato Tomoya, Nagai Yoshitaka, Imataka Hiroaki, Taguchi Hideki
期刊: | Journal of Biological Chemistry | 影响因子: | 3.900 |
时间: | 2025 | 起止号: | 2025 Apr;301(4):108360 |
doi: | 10.1016/j.jbc.2025.108360 |
特别声明
1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。
2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。
3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。
4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。