Transcription factors interact with RNA to regulate genes

• Published in: Molecular cell 2023-07, Vol.83 (14), p.2449-2463.e13
• Main Authors: Oksuz, Ozgur, Henninger, Jonathan E., Warneford-Thomson, Robert, Zheng, Ming M., Erb, Hailey, Vancura, Adrienne, Overholt, Kalon J., Hawken, Susana Wilson, Banani, Salman F., Lauman, Richard, Reich, Lauren N., Robertson, Anne L., Hannett, Nancy M., Lee, Tong I., Zon, Leonard I., Bonasio, Roberto, Young, Richard A.
• Format: Article
• Language: English
• Subjects: arginine-rich motif; Binding Sites; chromatin; development; DNA - genetics; gene regulation; Protein Binding; RNA; RNA - metabolism; RNA-binding proteins; single-molecule imaging; transcription factor; Transcription Factors - metabolism; zebrafish
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2023.06.012

Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function. [Display omitted] •Transcription factors (TFs) bind RNA•TFs harbor RNA-binding domains•TF-RNA binding promotes chromatin occupancy•TF-RNA binding is conserved, important for development, and disrupted in disease Oksuz et al. provide evidence that transcription factors frequently bind RNA at active loci, doing so with a conserved domain resembling the arginine-rich motif of the HIV Tat protein. TF-RNA binding constrains TF mobility in chromatin, contributes to gene regulation, is important for normal development, and, when defective, is involved in disease pathogenesis.