Transcription factors interact with RNA to regulate genes
Open accessPublished version of a preprint
Abstract
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.
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Metrics that summarize post-transcriptional regulation inevitably struggle to describe complex splicing outcomes, unannotated de novo events or the intricate and sometimes competitive relationship between transcription, splicing and intronic polyadenylation.
“However, such metrics inevitably struggle to describe complex splicing outcomes, unannotated de novo events or the intricate and sometimes competitive relationship between transcription, splicing and (intronic) polyadenylation24–26.”
From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [25]
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Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation
Linder, J., Srivastava, D., Yuan, H., Agarwal, V., & Kelley, D. R. (2025) · Nature Genetics · doi:10.1038/s41588-024-02053-6 · Cited by 265 · see citing works
- Authors
- Oksuz, O., Henninger, J. E., Warneford-Thomson, R., Zheng, M. M., Erb, H., Vancura, A., Overholt, K. J., Hawken, S. W., Banani, S. F., Lauman, R., Reich, L. N., Robertson, A. L., Hannett, N. M., Lee, T. I., Zon, L. I., Bonasio, R., & Young, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- University of Pennsylvania (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Corresponding author
- Young, Richard A.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2023-07
- Volume
- 83
- Issue
- 14
- Pages
- 2449-2463.e13
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC10529847
- OpenAlex
- W4382937503
- Cited by
- 275
- References
- 11
- Citations by year
- 2026: 65 · 2025: 91 · 2024: 89 · 2023: 28 · 2022: 2
- FWCI
- 24.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation (PHY2044895, 1745302, R01 HL144780-01, R24 OD017870-01)
- National Institutes of Health (GM144283, GM127408, GM138788, R01 HL144780-01, R24 OD017870-01)
- National Cancer Institute (F32CA254216, CA155258, CA251062)
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- Howard Hughes Medical Institute (JF549)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- transcription factors, RNA binding, gene expression regulation, chromatin, arginine-rich motif, HIV-1 Tat protein, transcriptional coactivator, corepressors, cell identity, vertebrate development, disease
- MeSH terms
- Binding Sites, DNA, Protein Binding, RNA, Transcription Factors
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