Open AccessSUPT4H1 Depletion Leads to a Global Reduction in RNA
Author(s) -
Adam Naguib,
Thomas Sandmann,
Fei Yi,
Ryan J. Watts,
Joseph W. Lewcock,
William E. Dowdle
Publication year - 2019
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2018.12.004
Subject(s) - rna polymerase ii , transcription (linguistics) , neurodegeneration , rna , transcriptome , biology , microbiology and biotechnology , transcription factor , amyotrophic lateral sclerosis , rna interference , rna polymerase , computational biology , genetics , gene expression , gene , disease , promoter , medicine , linguistics , philosophy , pathology
SUPT4H1 is a transcription elongation factor that makes up part of the RNA polymerase II complex. Recent studies propose a selective role for SUPT4H1 in the transcription of repeat-containing DNA, the translated products of which contribute to neurodegenerative disorders such as C9orf72-amyotrophic lateral sclerosis. To investigate the potential of SUPT4H1 as a therapeutic target in repeat-associated neurodegeneration, we depleted SUPT4H1 by RNA interference to inhibit the function of the SUPT4H1/SUPT5H transcription elongation complex. Depletion of SUPT4H1 leads to a global reduction in all cellular RNA, highlighting the significant challenges that are associated with targeting this molecule for the treatment of human disease. Any requirement of SUPT4H1 for transcription of specific transcripts should be interpreted in the context of global modulatory effects on the transcriptome.
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