Guo Pei, Chan Ho Yin Edwin, Lam Sik Lok
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
FEBS Lett. 2017 Jun;591(12):1752-1760. doi: 10.1002/1873-3468.12672. Epub 2017 May 27.
The expansion of CAG repeats has been found to be associated with at least nine human genetic disorders. In these disorders, the full-length expanded CAG RNA transcripts are cleaved into small CAG-repeated RNAs which are cytotoxic and known to be capable of forming hairpins. To better understand the RNA pathogenic mechanism, in this study we have performed high-resolution nuclear magnetic resonance structural investigations on the RNA hairpins formed by CAG repeats. Our results show the formation of a type III AGCA tetraloop and reveal the effect of stem rigidity on the loop conformational flexibility.
已发现CAG重复序列的扩增与至少九种人类遗传疾病有关。在这些疾病中,全长扩增的CAG RNA转录本被切割成具有细胞毒性且已知能够形成发夹结构的小CAG重复RNA。为了更好地理解RNA致病机制,在本研究中,我们对由CAG重复序列形成的RNA发夹进行了高分辨率核磁共振结构研究。我们的结果显示了III型AGCA四环的形成,并揭示了茎刚性对环构象灵活性的影响。