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Packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA depends upon conserved long-range interactions (LRIs) between U5 and gag sequences

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Kalloush, Rawan M., Vivet-Boudou, Valérie, Ali, Lizna M., Mustafa, Farah, Marquet, Roland, Rizvi, Tahir A.·2016·RNA
DOI 10.1261/rna.055731.115PMC PMC4878616
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Abstract

MPMV has great potential for development as a vector for gene therapy. In this respect, precisely defining the sequences and structural motifs that are important for dimerization and packaging of its genomic RNA (gRNA) are of utmost importance. A distinguishing feature of the MPMV gRNA packaging signal is two phylogenetically conserved long-range interactions (LRIs) between U5 and gag complementary sequences, LRI-I and LRI-II. To test their biological significance in the MPMV life cycle, we introduced mutations into these structural motifs and tested their effects on MPMV gRNA packaging and propagation. Furthermore, we probed the structure of key mutants using SHAPE (selective 2′hydroxyl acylation analyzed by primer extension). Disrupting base-pairing of the LRIs affected gRNA packaging and propagation, demonstrating their significance to the MPMV life cycle. A double mutant restoring a heterologous LRI-I was fully functional, whereas a similar LRI-II mutant failed to restore gRNA packaging and propagation. These results demonstrate that while LRI-I acts at the structural level, maintaining base-pairing is not sufficient for LRI-II function. In addition, in vitro RNA dimerization assays indicated that the loss of RNA packaging in LRI mutants could not be attributed to the defects in dimerization. Our findings suggest that U5-gag LRIs play an important architectural role in maintaining the structure of the 5′ region of the MPMV gRNA, expanding the crucial role of LRIs to the nonlentiviral group of retroviruses.

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  • Similar LRI-mediated RNA rearrangements have been observed in MPMV, FIV, and MMTV where complementary interactions between U5 and downstream sequences stabilize the overall RNA secondary structure facilitating gRNA packaging.

    “Similar LRI-mediated RNA rearrangements have been observed in MPMV, FIV, and MMTV where complementary interactions between U5 and downstream sequences stabilize the overall RNA secondary structure facilitating gRNA packaging”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Kalloush et al. 2016

    The Results and Discussion report that complementary U5–gag interactions help maintain the MPMV RNA structure and are important for genomic RNA packaging. The Discussion also identifies a comparable packaging-relevant interaction in FIV and notes LRIs in MMTV, but it does not establish that U5–downstream interactions stabilize RNA structure and facilitate packaging in MMTV specifically. The paper describes structural interactions rather than observed RNA rearrangements across all three viruses; page numbers were not supplied in our copy. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Kalloush, R. M., Vivet-Boudou, V., Ali, L. M., Mustafa, F., Marquet, R., & Rizvi, T. A.
Affiliations
  • United Arab Emirates University (AE)
  • Centre National de la Recherche Scientifique (FR)
ORCID
Venue
RNA
Publisher
Cold Spring Harbor Laboratory
Published
2016-04-19
Volume
22
Issue
6
Pages
905-919
ISSN
  • 1355-8382 (ISSN-L)
  • 1469-9001
DOI
10.1261/rna.055731.115
PMC
PMC4878616
OpenAlex
W2337622005
Cited by
17
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3
FWCI
1.39
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • RNA (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
  • univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion, cc-by-nc)
Funders
  • United Arab Emirates University (31M131)
  • College of Medicine and Health Sciences (NP/13/26)
  • UAEU-NRF (31M101)
  • Start-Up (31M122)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
Mason-Pfizer monkey virus, genomic RNA packaging, long-range interactions, RNA dimerization, RNA structure, gene therapy vectors, SHAPE probing, viral life cycle
MeSH terms
RNA, Viral, Genes, gag, Mason-Pfizer monkey virus, Virus Assembly

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