Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action
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The ability of the Rex protein of the type I human T-cell leukemia virus (HTLV-I) to regulate expression of the retroviral gag and env structural genes post-transcriptionally is critically dependent on the presence of a Rex response element (RexRE). This cis-regulatory sequence is located within the retroviral 3' long terminal repeat and coincides with a predicted, highly stable RNA stem-loop structure. Rex action requires both the overall secondary structure intrinsic to the RexRE and specific sequences from one small subregion of this large structure. This small subregion likely forms a protein-binding site for Rex or a cellular RNA-binding factor. Whereas Rex can functionally replace the Rev protein of the type 1 human immunodeficiency virus (HIV-1) through its interaction with the analogous Rev response element (RevRE), distinct subregions of this HIV-1 RNA element mediate the responses to Rex and Rev. Strikingly, Rex acts as a dominant repressor of Rev action, following the deletion of the Rex responsive subregion of the RevRE. Similarly, Rev inhibits Rex function in a dominant manner when the Rev responsive subregion of the RevRE is deleted. Together, these findings suggest that Rex and Rev not only interact with their respective RNA response elements but also may either form mixed inactive multimers or interact with a common cellular factor(s). If binding of a common host protein is involved, this factor likely plays a central role either in spliceosome assembly or nuclear RNA transport.
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Following Rex-RexRE interaction, RNAs are stabilized, splicing is inhibited, and they are exported via CRM1-dependent pathway.
“Following the interaction between Rex and RexRE, RNAs are stabilized, splicing is inhibited, and they are subsequently exported out of the nucleus via a CRM1-dependent cellular pathway (Fig. 9) (Ahmed et al. 1990, Grassmann et al. 1991, Hakata et al. 1998, 2001, 2003, Nakano and Watanabe 2012).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Ahmed et al. 1990
The Discussion (page unavailable) says Rex and RexRE are required for expression of proteins from unspliced or singly spliced viral RNA, and that Rex permits incompletely spliced RNA to appear in the cytoplasm. It describes effects on splicing, RNA stabilization, and nuclear transport as proposed mechanisms whose details remain unclear; it does not establish that Rex inhibits splicing or stabilizes these RNAs, or identify a CRM1-dependent export pathway. Its separate comment about RNA stability concerns fully spliced transcripts and polyadenylation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn HTLV-1, nuclear export of unspliced and singly spliced RNAs is controlled by RexRE.
“Similar to HIV-1, the nuclear export of unspliced and singly spliced RNAs in HTLV-1 is controlled by the Rex response element (RexRE).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Ahmed et al. 1990
RexRE is a cis-acting RNA stem-loop structural motif located within the 3′ LTR and interacts with Rex.
“The RexRE is a cis-acting RNA stem-loop structural motif located within the 3′ LTR and interacts with a virally encoded trans-acting protein called Rex (Fig. 9; Table 1) (Ahmed et al. 1990, Grassmann et al. 1991, Younis and Green 2005).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Ahmed et al. 1990
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- Authors
- Ahmed, Y. F., Hanly, S. M., Malim, M. H., Cullen, B. R., & Greene, W. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1990-06
- Volume
- 4
- Issue
- 6
- Pages
- 1014-1022
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2138851210
- Cited by
- 115
- References
- 41
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2019: 1 · 2017: 3 · 2016: 2 · 2014: 5 · 2013: 2 · 2012: 5
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- HIV-1 Rev protein, Rev response element, long terminal repeat, post-transcriptional regulation, RNA stem-loop structure, cis-regulatory elements, RNA-protein interactions, spliceosome assembly
- MeSH terms
- Animals, Haplorhini, Base Sequence, Cell Line, Molecular Sequence Data, Nucleic Acid Conformation, Precipitin Tests, Regulatory Sequences, Nucleic Acid, Repressor Proteins, RNA Splicing, RNA, Viral, Structure-Activity Relationship, Human T-lymphotropic virus 1, Trans-Activators, Gene Products, rev, Genes, gag, Genes, env, Gene Expression Regulation, Viral
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