Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target.
Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target.
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DOI：
10.1093/nar/gkr729
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Kozlowski P
中科院分区：
文献类型：
--
作者：
Krzyzosiak WJ;Sobczak K;Wojciechowska M;Fiszer A;Mykowska A;Kozlowski P
本文综述了三重重复序列RNA的结构，并在人类细胞中发挥的生理和致病作用的背景下，解决了正常和扩展长度的简单序列重复序列的详细信息。首先，我们讨论了转录本中各种三核苷酸重复的发生和频率，并根据形成不同结构和稳定性的RNA结构的倾向对其进行分类。我们发现，能够形成发夹结构的重复序列在外显子中过度表达，这意味着它们可能具有重要的功能。我们进一步描述了长的三联体重复RNA作为病原体，通过呈现由三联体重复扩增引起的人类神经系统疾病，其中突变体RNA获得毒性功能。这些疾病的突出实例包括强直性肌营养不良1型和脆性X相关震颤共济失调综合征，它们分别由突变的CUG和CGG重复序列触发。此外，我们还讨论了RNA介导的多聚谷氨酰胺疾病，如亨廷顿病和脊髓小脑共济失调3型，其中扩大CAG重复序列可能作为一个辅助毒性剂的发病机制。最后，三联体重复RNA作为治疗靶点。我们描述了各种概念和方法，旨在选择性抑制突变体转录活性的重复相关疾病的实验疗法。
This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in transcripts and classify them according to the propensity to form RNA structures of different architectures and stabilities. We show that repeats capable of forming hairpin structures are overrepresented in exons, which implies that they may have important functions. We further describe long triplet repeat RNA as a pathogenic agent by presenting human neurological diseases caused by triplet repeat expansions in which mutant RNA gains a toxic function. Prominent examples of these diseases include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome, which are triggered by mutant CUG and CGG repeats, respectively. In addition, we discuss RNA-mediated pathogenesis in polyglutamine disorders such as Huntington's disease and spinocerebellar ataxia type 3, in which expanded CAG repeats may act as an auxiliary toxic agent. Finally, triplet repeat RNA is presented as a therapeutic target. We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases.
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影响因子：
4.5
作者：
Daughters RS;Tuttle DL;Gao W;Ikeda Y;Moseley ML;Ebner TJ;Swanson MS;Ranum LP
通讯作者：
Ranum LP
影响因子：
5.6
作者：
Ciesiolka, J;Michalowski, D;Krzyzosiak, WJ
通讯作者：
Krzyzosiak, WJ
影响因子：
14.9
作者：
Fiszer A;Mykowska A;Krzyzosiak WJ
通讯作者：
Krzyzosiak WJ
影响因子：
3.5
作者：
Campuzano, V;Montermini, L;Koenig, M
通讯作者：
Koenig, M
DOI：
10.1073/pnas.0901824106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Arambula, Jonathan F.;Ramisetty, Sreenivasa Rao;Zimmerman, Steven C.
通讯作者：
Zimmerman, Steven C.