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The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation
Open accessAbstract
The mechanism of Tat transactivation was studied by treating cell lines containing Tat-defective viruses with purified Tat protein. These cell lines constitutively produce very low levels of virus in the absence of Tat, as measured by p24 antigen levels. Virus production can be increased greater than 30,000-fold by adding exogenous Tat. Tat addition increases mRNA levels early in the viral life cycle, and Tat is required for Rev function to become evident. There is no evidence for a translational effect of Tat. Nuclear run-on experiments show that the increase in mRNA levels is due to an increased efficiency of elongation of nascent transcripts. These results suggest that Tat may be a gene-specific elongation factor.
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Recruitment of the PAF complex via a flexible AFF4 scaffold ensures transcript elongation, providing the structural basis for the transition from pausing to active elongation.
“During this process, the recruitment of the PAF complex via a flexible AFF4 scaffold ensures transcript elongation, providing the structural basis for the transition from pausing to active elongation (Feinberg et al. 1991, Chou et al. 2013, Vos et al. 2020).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Feinberg et al. 1991
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A Third-Generation Lentivirus Vector with a Conditional Packaging System
Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., & Naldini, L. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8463-8471.1998 · Cited by 3,341
Beyond 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
“During this process, the recruitment of the PAF complex via a flexible AFF4 scaffold ensures transcript elongation, providing the structural basis for the transition from pausing to active elongation (Feinberg et al. 1991 , Chou et al. 2013 , Vos et al. 2020 ).”
Metadata
- Authors
- Feinberg, M. B., Baltimore, D., & Frankel, A. D.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1991-05
- Volume
- 88
- Issue
- 9
- Pages
- 4045-4049
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC51590
- OpenAlex
- W2072916562
- Cited by
- 365
- References
- 0
- Citations by year
- 2025: 6 · 2024: 11 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 15 · 2019: 4 · 2018: 4 · 2017: 9 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 7
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health (5u01ai026463-09)
- National Institute of General Medical Sciences (R01GM039458, GM-39458)
- National Institute of Allergy and Infectious Diseases (R01AI029135, AI 26463, AI29135)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- Tat protein, HIV-1, transcription elongation, transcriptional activation, viral life cycle, Rev protein, mRNA levels
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Line, Genetic Complementation Test, HeLa Cells, HIV, Humans, Molecular Sequence Data, RNA, Viral, Time Factors, Transcription, Genetic, Gene Products, tat, Gene Expression Regulation, Viral, tat Gene Products, Human Immunodeficiency Virus, In Vitro Techniques
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