Tat trans-activates the human immunodeficiency virus through a nascent RNA target
Abstract
Expression of the human immunodeficiency virus type 1 (HIV-1) genome is greatly dependent on the viral trans-activator protein Tat. Tat functions through the TAR element, which is represented in both viral DNA and RNA. At present, there is no definitive evidence that determines whether Tat acts through a DNA or RNA form of TAR. We have used an intramolecular mutagenesis approach to change selectively the RNA secondary structure of TAR without affecting its primary sequence. We show that a specific RNA secondary structure for TAR is needed for biological activity. Furthermore, transcripts that only transiently form a native TAR RNA hairpin, which is not maintained in the mature mRNA, are completely trans-activated by Tat, suggesting that TAR is recognized as a nascent RNA.
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The HIV-1 promoter region includes a TAR element with a stem-loop structural motif in the R region.
“For example, the HIV-1 promoter region includes a TAR element with a stem-loop structural motif in the R region (Fig. 8A).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Berkhout et al. 1989
In the absence of TAR-Tat interaction, transcription can initiate inefficiently and transcripts are not elongated, halting virus replication.
“In the absence of TAR–Tat interaction, transcription can initiate, though inefficiently, and transcripts are not elongated, halting virus replication (Fig. 8A).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Berkhout et al. 1989
The viral trans-activator Tat interacts with the TAR stem-loop motif, enhancing transcription and elongation of viral transcripts.
“The potent viral trans-activator Tat interacts with this stem-loop motif, enhancing the transcription and elongation of viral transcripts (Berkhout et al. 1989, Keen et al. 1997, Barboric and Peterlin 2005, Das et al. 2011, Schulze-Gahmen and Hurley 2018).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Berkhout et al. 1989
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Transcriptional and Posttranscriptional Regulation of HIV-1 Gene Expression
Karn, J., & Stoltzfus, C. M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006916 · Cited by 437 · see citing works
Das, A. T., Klaver, B., & Berkhout, B. (1995) · Journal of Virology · doi:10.1128/jvi.69.5.3090-3097.1995 · Cited by 149 · see citing works
Self-citationBeyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“The potent viral trans -activator Tat interacts with this stem-loop motif, enhancing the transcription and elongation of viral transcripts (Berkhout et al. 1989 , Keen et al. 1997 , Barboric and Pe-terlin 2005 , Das et al. 2011 , Schulze-Gahmen and Hurley 2018 ).”
- Authors
- Berkhout, B., Silverman, R. H., & Jeang, K.-T.
- Affiliations
- National Institute of Allergy and Infectious Diseases (US)
- Uniformed Services University of the Health Sciences (US)
- National Institutes of Health (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1989-10
- Volume
- 59
- Issue
- 2
- Pages
- 273-282
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2072528655
- Cited by
- 647
- References
- 0
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 14 · 2019: 11 · 2018: 12 · 2017: 13 · 2016: 11 · 2015: 7 · 2014: 18 · 2013: 12 · 2012: 12
- FWCI
- 11.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- National Institutes of Health
- Uniformed Services University of the Health Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HIV-1, TAR element, nascent RNA, RNA secondary structure, RNA hairpin, transcriptional activation, HIV-1 gene expression
- MeSH terms
- Animals, Base Sequence, Cell Line, Enhancer Elements, Genetic, Genes, Viral, Molecular Sequence Data, Mutation, Plasmids, RNA, RNA, Messenger, RNA, Viral, Transcription, Genetic, Virus Activation, HIV-1, Trans-Activators, Viral Structural Proteins, Gene Products, tat, Gene Expression, Gene Expression Regulation, Viral, RNA, Antisense, tat Gene Products, Human Immunodeficiency Virus
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