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Gene regulation

RNA binding — a useful third wheel in transcription

Nature Reviews Molecular Cell Biology volume 24, page 604 (2023)Cite this article

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Transcription factors (TFs) are considered to have two functional domains — a DNA-binding domain, with which they bind to enhancers and promoters, and a protein-binding domain. Although non-coding RNA molecules are produced at enhancers and promoters in proximity to TF binding sites, TFs do not have ‘canonical’ RNA-binding domains, and the role of these RNAs in transcription is debated. Oksuz, Henninger et al. now show that various TFs indeed bind RNA — through a specific motif — and that this interaction can promote transcription and has a role in development and disease.

Various TFs that showed evidence of binding RNA in cells were next purified from human cells and had their RNA-binding affinity measured in vitro. Interestingly, the TF binding affinity for RNA was remarkably similar to that of known RNA-binding proteins and were sequence-independent. Analysis of amino acid features revealed enrichment in TFs of a motif similar to the RNA-binding domain of the HIV transcription factor Tat, known as the Arginine-rich motif (ARM). These TF ARM-like domains (TF-ARMs) have evolutionarily conserved sequences, despite their proximity to diverse types of DNA-binding domains in various TFs.

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  1. Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/

    Eytan Zlotorynski

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  1. Eytan Zlotorynski
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Correspondence to Eytan Zlotorynski.

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Zlotorynski, E. RNA binding — a useful third wheel in transcription. Nat Rev Mol Cell Biol 24, 604 (2023). https://doi.org/10.1038/s41580-023-00643-6

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  • DOI: https://doi.org/10.1038/s41580-023-00643-6

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