Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
Hum Mol Genet. 2011 Oct 1;20(19):3811-21. doi: 10.1093/hmg/ddr299. Epub 2011 Jul 4.
Discrete and punctate nuclear RNA foci are characteristic molecular hallmarks of pathogenesis in myotonic dystrophy type 1 and type 2. Intranuclear RNA inclusions of distinct morphology have also been found in fragile X-associated tremor ataxia syndrome, Huntington's disease-like 2, spinocerebellar ataxias type 8, type 10 and type 31. These neurological diseases are associated with the presence of abnormally long simple repeat expansions in their respective genes whose expression leads to the formation of flawed transcripts with altered metabolisms. Expanded CUG, CCUG, CGG, CAG, AUUCU and UGGAA repeats are associated with the diseases and accumulate in nuclear foci, as demonstrated in variety of cells and tissues of human and model organisms. These repeat RNA foci differ in size, shape, cellular abundance and protein composition and their formation has a negative impact on cellular functions. This review summarizes the efforts of many laboratories over the past 15 years to characterize nuclear RNA foci that are recognized as important triggers in the mutant repeat RNA toxic gain-of-function mechanisms of pathogenesis in neurological disorders.
离散点状核 RNA 焦点是肌强直性营养不良 1 型和 2 型发病机制的特征分子标志。在脆性 X 相关震颤共济失调综合征、亨廷顿病样 2、脊髓小脑共济失调 8 型、10 型和 31 型中，也发现了具有独特形态的核内 RNA 包涵体。这些神经疾病与各自基因中异常长的简单重复扩展的存在有关，其表达导致具有改变代谢的有缺陷的转录物的形成。扩展的 CUG、CCUG、CGG、CAG、AUUCU 和 UGGAA 重复与这些疾病有关，并在核焦点中积累，如在人类和模式生物的各种细胞和组织中所证明的那样。这些重复 RNA 焦点在大小、形状、细胞丰度和蛋白质组成上有所不同，其形成对细胞功能有负面影响。本综述总结了过去 15 年来许多实验室的努力，以表征核 RNA 焦点，这些焦点被认为是神经紊乱发病机制中突变重复 RNA 毒性获得功能机制的重要触发因素。
