Cell Reports
Volume 26, Issue 1, 2 January 2019, Pages 45-53.e4
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SUPT4H1 Depletion Leads to a Global Reduction in RNA

https://doi.org/10.1016/j.celrep.2018.12.004Get rights and content
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Highlights

  • SUPT4H1 is required for maintenance of steady-state RNA levels

  • Therapeutic targeting of SUPT4H1 needs to consider global effects on transcription

Summary

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.

Keywords

SUPT4H1
transcription
neurodegeneration
amyotrophic lateral sclerosis
ALS
di-amino acid repeats
DARPs

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