CAG三核苷酸RNA重复序列溶液结构的核磁共振研究

人基因组中CAG（胞嘧啶-腺嘌呤-鸟嘌呤）三核苷酸重复序列的扩增突变导致共计10种神经退行性疾病。近年来的研究发现转录产生扩增的CAG RNA，其形成特定的空间结构进而造成细胞毒性，靶向结合CAG RNA的小分子有望成为治疗相关疾病的药物。目前尚缺乏对CAG RNA溶液结构的深入研究和认识。本项目拟利用液体核磁共振技术研究不同链长的纯重复CAG RNA的溶液结构，并测定其高分辨率三维空间结构。基于此，以促进CAG RNA致病机制的研究，并为靶向CAG RNA小分子药物的设计提供准确的结构信息，对于相关神经退行性疾病的发生机制研究和药物研发具有较高的理论和应用价值。

CAG (cytosine-adenine-guanine) trinucleotide repeat expansions in the human genome have been found to cause 10 neurodegenerative diseases. Recent research progress reveals that the expanded CAG RNA transcripts can form secondary or tertiary structures and induce cellular toxicities, and small molecules targeting CAG RNA are promising drug candidates for disease therapy. Yet, there is a lack of deep investigation and understanding on solution structures of CAG RNA. This project aims to investigate the solution structures of CAG RNA with different chain lengths, and to determine the high-resolution three-dimensional structures of CAG RNA. Results of this project will facilitate further studies on disease-causing pathways involving CAG RNA and provide accurate structural information for drug design, possessing relatively high theoretical and practical values in understanding disease pathogenesis and developing therapeutics.