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Promoter Complex in the Central Part of the Mouse Mammary Tumor Virus Long Terminal Repeat
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Unique among the retroviruses, mouse mammary tumor virus (MMTV) carries, in addition to the usual long terminal repeat (LTR) promoter, another promoter, P2, which is located in the central part of the proviral U3 sequence, within the LTR open reading frame (ORF). Using an in vitro reporter system based on a sensitive luciferase expression assay, we investigated the regulation of the P2 promoter in the context of the Mtv-2 and Mtv-8 genomes. Irrespective of the genomic source, the activity of the P2 promoter is regulated by a downstream-located enhancer and an upstream-located negative regulatory element (NRE), the activity of which overrides the activator. During this study, we unexpectedly detected another independent neighboring promoter that we called P3. The novel P3 promoter does not seem to be controlled by any NRE but is influenced by the same enhancer that modulates the P2 promoter. The respective transcription starts of the two promoters located in this tight cluster are only 61 bases apart. The transcripts originating from this promoter complex carry the same first intron, which is bound by canonical splice donor and splice acceptor sites located in the LTR. One novel doubly spliced transcript carrying a 459-nucleotide-long ORF was detected in several MMTV-carrying murine cells and could be successfully expressed in murine cells as a His-tagged fusion product. The novel viral protein, the function of which remains to be elucidated, has an apparent molecular mass of 20 kDa.
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The first U3 promoter (P1) is the classical promoter near the U3-R border, while the other two U3 promoters are found approximately 650 and 415 nts upstream of P1.
“The first U3 promoter (P1) is the classical promoter near the U3-R border, while the other two promoters are found ∼650 and 415 nts upstream of P1, respectively (Rouault et al. 2007).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Rouault et al. 2007
MMTV has multiple promoters, with three reported within U3 and two reported within env.
“In the case of MMTV, multiple promoters have been described, with three reported within U3, while two reported within env.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Rouault et al. 2007
All three U3 promoters have the potential to transcribe known MMTV genes, including sag.
“All three U3 promoters have the potential to transcribe the known MMTV genes, including sag,”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Rouault et al. 2007
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Wnt Signaling in Mammary Glands: Plastic Cell Fates and Combinatorial SignalingPreprint
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“The first U3 promoter (P1) is the classical promoter near the U3-R border, while the other two promoters are found ∼ 650 and 415 nts upstream of P1, respectively (Rouault et al. 2007 ) .”
Commentary: With a little help from my enteric microbial friends
Günzburg, W. H., & Salmons, B. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.01029 · Cited by 1
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Metadata
- Authors
- Rouault, F., Nejad Asl, S. B., Rungaldier, S., Fuchs, E., Salmons, B., & Günzburg, W. H.
- Affiliations
- Austrianova Biomanufacturing AG
- Christian Doppler Laboratory for Gene Therapeutic Vector Development
- University of Veterinary Medicine Vienna (AT)
- ORCID
- Salmons, Brian
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2007-11-15
- Volume
- 81
- Issue
- 22
- Pages
- 12572-12581
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2169016
- OpenAlex
- W2123064717
- Cited by
- 5
- References
- 40
- Citations by year
- 2025: 1 · 2018: 1 · 2015: 1 · 2012: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- mouse mammary tumor virus, long terminal repeat, P2 promoter, promoter complex, negative regulatory element, enhancers, transcriptional regulation, U3 region, introns, splicing, viral proteins
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Luciferases, Mammary Tumor Virus, Mouse, Molecular Sequence Data, Promoter Regions, Genetic, Transcription, Genetic, Protein Biosynthesis, Viral Proteins, Gene Expression Regulation, Viral, Open Reading Frames, Genes, Reporter, Terminal Repeat Sequences, RNA Splice Sites, Transcription Initiation Site, Mice
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