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Cited by 15RNA Research and SplicingT-cell and Retrovirus StudiesRNA and protein synthesis mechanisms

A purine loop and the primer binding site are critical for the selective encapsidation of mouse mammary tumor virus genomic RNA by Pr77Gag

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Chameettachal, Akhil, Vivet-Boudou, Valérie, Pitchai, Fathima Nuzra Nagoor, Pillai, Vineeta N, Ali, Lizna Mohamed, Krishnan, Anjana, Bernacchi, Serena, Mustafa, Farah +2 more·2021·Nucleic Acids Research
DOI 10.1093/nar/gkab223PMC PMC8096270
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Abstract

Retroviral RNA genome (gRNA) harbors cis-acting sequences that facilitate its specific packaging from a pool of other viral and cellular RNAs by binding with high-affinity to the viral Gag protein during virus assembly. However, the molecular intricacies involved during selective gRNA packaging are poorly understood. Binding and footprinting assays on mouse mammary tumor virus (MMTV) gRNA with purified Pr77Gag along with in cell gRNA packaging study identified two Pr77Gag binding sites constituting critical, non-redundant packaging signals. These included: a purine loop in a bifurcated stem-loop containing the gRNA dimerization initiation site, and the primer binding site (PBS). Despite these sites being present on both unspliced and spliced RNAs, Pr77Gag specifically bound to unspliced RNA, since only that could adopt the native bifurcated stem–loop structure containing looped purines. These results map minimum structural elements required to initiate MMTV gRNA packaging, distinguishing features that are conserved amongst divergent retroviruses from those perhaps unique to MMTV. Unlike purine-rich motifs frequently associated with packaging signals, direct involvement of PBS in gRNA packaging has not been documented in retroviruses. These results enhance our understanding of retroviral gRNA packaging/assembly, making it not only a target for novel therapeutic interventions, but also development of safer gene therapy vectors.

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  • Structural occlusions have been observed in spliced RNAs of MMTV, MPMV, and FIV.

    “Such structural occlusions have recently been observed in spliced RNAs of MMTV, MPMV, and FIV”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Chameettachal et al. 2021

    The Discussion (page unavailable) reports that in spliced MMTV env and sag RNAs, the ssPurines become base-paired and unavailable for Gag binding, supporting structural occlusion in MMTV. The paper does not report comparable observations in spliced MPMV or FIV RNAs; its Introduction mentions those viruses in a different context. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A recent study reported that the PBS is involved in packaging of MMTV gRNA.

    “In addition to its pivotal role in the initiation of reverse transcription, a recent study reported the involvement of PBS in the packaging of MMTV gRNA (Chameettachal et al. 2021).”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Chameettachal et al. 2021

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Cited by

Sorted by citations

Authors
Chameettachal, A., Vivet-Boudou, V., Pitchai, F. N. N., Pillai, V. N., Ali, L. M., Krishnan, A., Bernacchi, S., Mustafa, F., Marquet, R., & Rizvi, T. A.
Affiliations
  • United Arab Emirates University (AE)
  • Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, UPR 9002, Strasbourg, France
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Marquet, Roland
  • Rizvi, Tahir A
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2021-04-09
Volume
49
Issue
8
Pages
4668-4688
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkab223
PMC
PMC8096270
OpenAlex
W3147695599
Cited by
15
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 1
FWCI
0.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • United Arab Emirates University (UCBR-31R123)
  • College of Medicine and Health Sciences (31M280)
  • CNRS
  • UAEU (UCBR-31R123, UPAR-31M233)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
mouse mammary tumor virus, genomic RNA packaging, primer binding site, unspliced RNA, RNA-protein interactions, RNA structure, retroviral assembly, gene therapy vectors
MeSH terms
Dynamic Light Scattering, Animals, Binding Sites, Mammary Tumor Virus, Mouse, Nucleic Acid Conformation, Purines, RNA Splicing, RNA, Viral, Gene Products, gag, Genome, Viral, DNA Primers, Virus Assembly, Mice, Real-Time Polymerase Chain Reaction

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