Repeat-associated non-ATG (RAN) translation in neurological disease.
Repeat-associated non-ATG (RAN) translation in neurological disease.
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DOI：
10.1093/hmg/ddt371
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发表时间：
2013-10-15
影响因子：
3.5
通讯作者：
Ranum LP
中科院分区：
文献类型：
--
作者：
Cleary JD;Ranum LP
成熟的翻译起始规则已被用作分子生物学的基石，以了解基因表达，并构建关于细胞合成什么蛋白质、蛋白质如何工作以及预测突变后果的基本问题。对于一组由DNA短片段的异常扩张(如CAG·CTG重复)引起的神经系统疾病，预测编码区和非编码区内外的突变被认为是通过蛋白质获得或功能丧失或RNA功能获得的机制而引起的。与这些预测相反，最近发现的重复相关非ATG(RAN)翻译表明，扩展突变可以在没有Aug起始密码子的情况下在所有三个阅读框架中表达同源多聚体扩展蛋白。这种意想不到的、非规范类型的蛋白质翻译依赖于长度和发夹，不需要移码或RNA编辑，并且发生在各种重复基序中。到目前为止，RAN蛋白已在脊髓小脑型共济失调8型(SCA8)、强直性肌营养不良1型(DM1)、脆性X震颤共济失调综合征(FXTAS)和C9ORF72肌萎缩侧索硬化症/额颞叶痴呆(ALS/FTD)中被报道。在这篇文章中，我们回顾了目前已知的RAN翻译及其在理解其对疾病的贡献方面的最新进展。
Well-established rules of translational initiation have been used as a cornerstone in molecular biology to understand gene expression and to frame fundamental questions on what proteins a cell synthesizes, how proteins work and to predict the consequences of mutations. For a group of neurological diseases caused by the abnormal expansion of short segments of DNA (e.g. CAG•CTG repeats), mutations within or outside of predicted coding and non-coding regions are thought to cause disease by protein gain- or loss-of-function or RNA gain-of-function mechanisms. In contrast to these predictions, the recent discovery of repeat-associated non-ATG (RAN) translation showed expansion mutations can express homopolymeric expansion proteins in all three reading frames without an AUG start codon. This unanticipated, non-canonical type of protein translation is length-and hairpin-dependent, takes place without frameshifting or RNA editing and occurs across a variety of repeat motifs. To date, RAN proteins have been reported in spinocerebellar ataxia type 8 (SCA8), myotonic dystrophy type 1 (DM1), fragile X tremor ataxia syndrome (FXTAS) and C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). In this article, we review what is currently known about RAN translation and recent progress toward understanding its contribution to disease.
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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：
16.2
作者：
Ash PE;Bieniek KF;Gendron TF;Caulfield T;Lin WL;Dejesus-Hernandez M;van Blitterswijk MM;Jansen-West K;Paul JW 3rd;Rademakers R;Boylan KB;Dickson DW;Petrucelli L
通讯作者：
Petrucelli L
影响因子：
12.7
作者：
Al-Sarraj, Safa;King, Andrew;Shaw, Christopher E.
通讯作者：
Shaw, Christopher E.
DOI：
10.1073/pnas.1207846109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Lee, Sooncheol;Liu, Botao;Qian, Shu-Bing
通讯作者：
Qian, Shu-Bing
影响因子：
30.8
作者：
Koob, MD;Moseley, ML;Ranum, LPW
通讯作者：
Ranum, LPW