@article{dca212fbcb0a4f45b8a2116294a3615a,
title = "Spt4 is selectively required for transcription of extended trinucleotide repeats",
abstract = "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.",
author = "Liu, {Chia Rung} and Chang, {Chuang Rung} and Yijuang Chern and Wang, {Tzu Han} and Hsieh, {Wen Chieh} and Shen, {Wen Chuan} and Chang, {Chi Yuan} and Chu, {I. Chieh} and Ning Deng and Cohen, {Stanley N.} and Cheng, {Tzu Hao}",
note = "Funding Information: We thank Chih-Yen King, Fang-Jen Lee, Jing-Jer Lin, Michael Sherman, Michael Snyder, Elena Cattaneo, Marcy MacDonald, and the HD Community BioRepository ( http://ccr.coriell.org ) sponsored by CHDI Foundation for providing experimental materials. We thank Cheng-Fu Kao for technical assistance in the ChIP assay and Yong Cheng, Zhihai Ma, Mark McCreary, and Richard Lin for assistance in compilation and analysis of RNA-seq data. T.-H.C. received grants from National Science Council (NSC- 96-2311-B-010-001 and NSC-98-2311-B-010-001-MY3), and the “Aim for the Top University Plan” grant from the Ministry of Education of the Republic of China. S.N. Cohen and N. Deng received support from Kwoh-Ting Li Professorship funds endowed by the Friends of Stanford Foundation of Taiwan. ",
year = "2012",
month = feb,
day = "17",
doi = "10.1016/j.cell.2011.12.032",
language = "English",
volume = "148",
pages = "690--701",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "4",
}