通过微小 RNA 实现 UTT 控制：精细调节 ATXN1 水平以预防共济失调。
UTteR control through miRs: fine-tuning ATXN1 levels to prevent ataxia.
机构信息
Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, Florida 32610, USA.
Department of Molecular Genetics and Microbiology, Center for NeuroGenetics, the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA.
出版信息
Genes Dev. 2020 Sep 1;34(17-18):1107-1109. doi: 10.1101/gad.343020.120.
Pathomechanistic studies of neurodegenerative diseases have documented the toxic effects of mutant protein expression, misfolding, and aggregation. However, alterations in the expression of the corresponding wild-type (WT) gene, due to either variations in copy number or transcriptional regulation, have also been linked to Alzheimer's and Parkinson's diseases. Another striking example of this mutant and WT duality is spinocerebellar ataxia type 1 (SCA1) caused by an ATXN1 polyglutamine protein, although subtle variations in WT AXTN1 levels also lead to ataxia. In this issue of , Nitschke and colleagues (pp. 1147-1160) delve into posttranscriptional events that fine-tune ATXN1 expression and uncover a key role for 5' untranslated region (5' UTR)-miR760 interactions. Thus, this study not only provides significant insights into the complexities of modulating the expression of a dosage-sensitive gene but also highlights the critical importance of identifying noncoding polymorphisms as disease risk factors.
神经退行性疾病的病理机制研究记录了突变蛋白表达、错误折叠和聚集的毒性作用。然而，相应的野生型（WT）基因表达的改变，由于拷贝数或转录调节的变化，也与阿尔茨海默病和帕金森病有关。这种突变和 WT 双重性的另一个显著例子是由 ATXN1 多聚谷氨酰胺蛋白引起的脊髓小脑共济失调 1 型（SCA1），尽管 WT AXTN1 水平的细微变化也会导致共济失调。在本期的 中，Nitschke 及其同事（第 1147-1160 页）深入研究了微调 ATXN1 表达的转录后事件，并揭示了 5'非翻译区（5'UTR）-miR760 相互作用的关键作用。因此，这项研究不仅为调节剂量敏感基因的表达的复杂性提供了重要的见解，还强调了确定非编码多态性作为疾病风险因素的关键重要性。
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