Spt4 is selectively required for transcription of extended trinucleotide repeats

Chia Rung Liu, Chuang Rung Chang, Yijuang Chern, Tzu Han Wang, Wen Chieh Hsieh, Wen Chuan Shen, Chi Yuan Chang, I. Chieh Chu, Ning Deng, Stanley N. Cohen*, Tzu Hao Cheng

*此作品的通信作者

研究成果: Article同行評審

84 引文 斯高帕斯(Scopus)

摘要

Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders. Using a phenotypic screen to identify events that restore functionality to polyQ proteins in S. cerevisiae, we discovered that transcription elongation factor Spt4 is required to transcribe long trinucleotide repeats located either in ORFs or nonprotein-coding regions of DNA templates. Mutation of SPT4 selectively decreased synthesis of and restored enzymatic activity to expanded polyQ protein without affecting protein lacking long-polyQ stretches. RNA-seq analysis revealed limited effects of Spt4 on overall gene expression. Inhibition of Supt4h, the mammalian ortholog of Spt4, reduced mutant huntingtin protein in neuronal cells and decreased its aggregation and toxicity while not altering overall cellular mRNA synthesis. Our findings identify a cellular mechanism for transcription through repeated trinucleotides and a potential target for countermeasures against neurological disorders attributable to expanded trinucleotide regions.

原文English
頁(從 - 到)690-701
頁數12
期刊Cell
148
發行號4
DOIs
出版狀態Published - 17 2月 2012

指紋

深入研究「Spt4 is selectively required for transcription of extended trinucleotide repeats」主題。共同形成了獨特的指紋。

引用此