Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a complex retrovirus

Mertz, Jennifer A.; Simper, Melissa S.; Lozano, Mary M.; Payne, Shelley M.; Dudley, Jaquelin P.

doi:10.1128/jvi.79.23.14737-14747.2005

Cited by 130T-cell and Retrovirus StudiesRNA Research and SplicingHIV Research and Treatment

Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a complex retrovirus

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Mertz, Jennifer A., Simper, Melissa S., Lozano, Mary M., Payne, Shelley M., Dudley, Jaquelin P.·2005·Journal of Virology

DOI 10.1128/jvi.79.23.14737-14747.2005PMC PMC1287593

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Abstract

Mouse mammary tumor virus (MMTV) has been classified as a simple retrovirus with two accessory genes,dut and sag. Cloned MMTV proviruses carrying a trimethoprim (trim) cassette in the envelope gene were defective for Gag protein production and the nuclear export of unspliced gag-pol RNA. Complementation experiments indicated that a trans-acting product was responsible for the Gag defect of such mutants. Analysis of MMTV-infected cells revealed the presence of a novel, doubly spliced RNA that encodes a putative product of 301 amino acids. Overexpression of cDNA from this RNA increased Gag levels from env mutant proviruses or reporter gene expression from unspliced mRNAs and allowed detection of a 33-kDa protein product, which has been named r egulator of e xport of MMTV m RNA, or Rem. The Rem N terminus has motifs similar to the Rev-like export proteins of complex retroviruses, and mutation of the nuclear localization signal (NLS) abolished RNA export and detection within the nucleus. The Rem C terminus has few identifiable features, but removal of this domain increased Rem-mediated export, suggesting an autoregulatory function. A reporter vector developed from the 3′ end of the MMTV provirus was Rem responsive and required both the presence of the MMTV env-U3 junction and a functional Crm1 pathway. The identification of a third accessory protein from a doubly spliced transcript suggests that MMTV is the first murine complex retrovirus to be documented. Manipulation of the MMTV genome may provide mouse models for human retroviral diseases, such as AIDS.

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MMTV encodes Rem, which interacts with RmRE present at the 3′ end of the genome within the env gene, overlapping the 3′ LTR.
“Similarly, MMTV encodes a protein called Regulator of Export of MMTV mRNA (Rem), which interacts with the Rem Responsive Element (RmRE) present at the 3′end of the genome within the env gene, but overlapping the 3′ LTR.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Mertz et al. 2005
RmRE is found in both unspliced and spliced RNAs.
“Like HIV-1, this element is found in both the unspliced and spliced RNAs (Fig. 9; Table 1) (Indik et al. 2005, Mertz et al. 2005, 2009, Müllner et al. 2008).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Mertz et al. 2005

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Articles of Significant Interest Selected from This Issue by the Editors
(2005) · Journal of Virology · doi:10.1128/jvi.79.23.14471-14472.2005
Characterisation of mouse mammary tumour virus and host related regulatory factors
Müllner, M. (2012)
Identification of the Rem-responsive element of mouse mammary tumor virus
Mullner, M., Salmons, B., Gunzburg, W. H., & Indik, S. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn608 · Cited by 34 · see citing works
A novel, mouse mammary tumor virus encoded protein with Rev-like properties
Indik, S., Günzburg, W. H., Salmons, B., & Rouault, F. (2005) · Virology · doi:10.1016/j.virol.2005.03.040 · Cited by 99 · see citing works
Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element
Mertz, J. A., Lozano, M. M., & Dudley, J. P. (2009) · Retrovirology · doi:10.1186/1742-4690-6-10 · Cited by 37 · see citing works
Self-citation

Authors: Mertz, J. A., Simper, M. S., Lozano, M. M., Payne, S. M., & Dudley, J. P.
Affiliations: The University of Texas at Austin (US)
Corresponding author: Dudley, Jaquelin P.
ORCID: Mertz, Jennifer A.
Payne, Shelley M.
Dudley, Jaquelin P.
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2005-12-15
Volume: 79
Issue: 23
Pages: 14737-14747
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.79.23.14737-14747.2005
PMC: PMC1287593
OpenAlex: W2109377528
Cited by: 130
References: 58
Citations by year: 2026: 3 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 12 · 2014: 6 · 2013: 6 · 2012: 8
FWCI: 1.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (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: mouse mammary tumor virus, RNA export, nuclear export, Gag protein, accessory genes, nuclear localization signal, murine retrovirus
MeSH terms: Animals, Mammary Tumor Virus, Mouse, RNA, Viral, Viral Proteins, Mice

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Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a complex retrovirus

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