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Cited by 13RNA Research and SplicingRNA and protein synthesis mechanismsT-cell and Retrovirus Studies

A cis-acting element downstream of the mouse mammary tumor virus major splice donor critical for RNA elongation and stability

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Akhlaq, Shaima, Panicker, Neena G., Philip, Pretty S., Ali, Lizna M., Dudley, Jaquelin P., Rizvi, Tahir A., Mustafa, Farah·2018·Journal of Molecular Biology
DOI 10.1016/j.jmb.2018.08.025PMC PMC6193448
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Abstract

BACKGROUND: The mouse mammary tumor virus (MMTV) encodes a functional signal peptide, a cleavage product of envelope and Rem proteins. Signal peptide interacts with a 3' cis-acting RNA element, the Rem-responsive element (RmRE), to facilitate expression of both unspliced genomic (gRNA) and spliced mRNAs. An additional RmRE has been proposed at the 5' end of the genome, facilitating nuclear export of the unspliced gRNA, whereas the 3' RmRE could facilitate translation of all other mRNAs, including gRNA. RESULTS: To address this hypothesis, a series of mutations were introduced into a 24-nt region found exclusively in the unspliced gRNA. Mutant clones using MMTV or human cytomegalovirus promoters were tested in both transient and stable transfections to determine their effect on gRNA nuclear export, stability, and translation. Nuclear export of the gRNA was affected only in a small mutant subset in stably transfected Jurkat T cells. Quantitative real-time RT-PCR of actinomycin D-treated cells expressing MMTV revealed that multiple mutants were severely compromised for RNA expression and stability. Both genomic and spliced nuclear RNAs were reduced, leading to abrogation of Gag and Env protein expressed from unspliced and spliced mRNAs, respectively. RT-PCRs with multiple primer pairs indicated failure to elongate genomic MMTV transcripts beyond ~500 nt compared to the wild type in a cell line-dependent manner. CONCLUSIONS: MMTV contains a novel cis-acting element downstream of the major splice donor critical for facilitating MMTV gRNA elongation and stability. Presence of a mirror repeat within the element may represent important viral/host factor binding site(s) within MMTV gRNA.

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  • Recent studies on MMTV identified a novel 12-nt-long cis-acting element located immediately downstream of the major splice donor that is crucial for MMTV gRNA transcription, elongation, and stability.

    “Recent studies on MMTV have identified a novel 12-nt-long cis-acting element located immediately downstream of the major splice donor, which is crucial for MMTV gRNA transcription, elongation, and stability (Fig. 8B) (Akhlaq et al. 2018).”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Akhlaq et al. 2018

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Authors
Akhlaq, S., Panicker, N. G., Philip, P. S., Ali, L. M., Dudley, J. P., Rizvi, T. A., & Mustafa, F.
Affiliations
  • United Arab Emirates University (AE)
  • The University of Texas at Austin (US)
Corresponding author
  • Dudley, Jaquelin P.
  • Rizvi, Tahir A.
  • Mustafa, Farah
ORCID
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2018-10
Volume
430
Issue
21
Pages
4307-4324
ISSN
0022-2836 (ISSN-L)
DOI
10.1016/j.jmb.2018.08.025
PMC
PMC6193448
OpenAlex
W2889527131
Cited by
13
References
3
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 1
FWCI
0.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Biology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • United Arab Emirates University Zayed Center for Health Sciences (31R020, 31R122, 31R140)
  • Terry Fox Funds for Cancer Research (21M095)
  • College of Medicine & Health Sciences (NP 14-34)
  • National Institutes of Health (CA167053)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
mouse mammary tumor virus, cis-acting RNA elements, RNA splicing, RNA stability, RNA elongation, nuclear export, genomic RNA, spliced mRNA
MeSH terms
Animals, Cytomegalovirus, Dactinomycin, Humans, Mammary Tumor Virus, Mouse, Mutation, Promoter Regions, Genetic, RNA Splicing, RNA, Viral, Jurkat Cells, RNA Stability, Active Transport, Cell Nucleus, Mice

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