RNA‐centric world of retroviruses: unravelling the molecular strategies of genomic RNA packaging
- 1Department of Microbiology & Immunology, College of Medicine and Health Sciences (CMHS) United Arab Emirates University (UAEU) Al Ain 15551 UAE
- 2Department of Biochemistry & Molecular Biology, College of Medicine and Health Sciences (CMHS) United Arab Emirates University (UAEU) Al Ain 15551 UAE
- 3Zayed bin Sultan Center for Health Sciences (ZCHS) United Arab Emirates University Al Ain Al Ain UAE
Abstract
Retroviruses constitute a unique group of RNA viruses that have profoundly influenced both evolutionary trajectories and biomedical research. Their ability to reverse transcribe and integrate into host genomes has shaped genomic architecture across species and contributed to our understanding of oncogenes, gene regulation, and RNA biology. This review provides an in‐depth examination of retroviral molecular biology, beginning with the intricacies of their genome organization. We present an in‐depth discussion of the complex interplay of cis‐ and trans‐acting RNA elements during retrovirus replication, ending with a focus on genomic RNA packaging as the basis of infectious virion production. Emphasis is placed on how, among the various viral proteins, it is the retroviral Gag (Group‐specific antigen) that selectively orchestrates the packaging of the unspliced RNA amid a background of cellular and spliced viral RNAs. This is followed by our current understanding of how this process is affected by the retroviral Gag/Pol (Polymerase) and Gag/Pro (Protease)/Pol precursor proteins in the context to which the actual virion assembly takes place. Next, the review outlines emerging concepts regarding the structural basis of RNA recognition, the pivotal role of unpaired purines and long‐range intragenomic interactions (LRIs), in guiding genome selection. It discusses the dynamic processes of RNA dimerization and how it is not just intricately linked but is a pre‐requisite for genomic RNA encapsidation. Special attention is given to the new findings on transcription start site heterogeneity, cap sequestration, and epitranscriptomic modifications in shaping the fate of retroviral RNAs between translation and packaging since both these processes are critical for a successful viral life cycle. The review also addresses the involvement of assembly intermediates, and liquid–liquid phase separation in orchestrating efficient genome packaging and virus maturation. By integrating classical discoveries with recent findings, the review underscores the sophistication of retrovirus replication and proposes new avenues of research for therapeutic targeting of genome packaging and steps of viral assembly.
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BibTeX
@article{jehad2026rnacentric,
title = {{RNA‐centric world of retroviruses: unravelling the molecular strategies of genomic RNA packaging}},
author = {Mohammad Abdullah Jehad and Suresha G. Prabhu and Lizna M. Ali and Vineeta N. Pillai and Farah Mustafa and Tahir A. Rizvi},
journal = {Biological Reviews of the Cambridge Philosophical Society},
year = {2026},
month = may,
doi = {10.1002/brv.70188},
url = {https://doi.org/10.1002/brv.70188},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RNA‐centric world of retroviruses: unravelling the molecular strategies of genomic RNA packaging
AU - Mohammad Abdullah Jehad
AU - Suresha G. Prabhu
AU - Lizna M. Ali
AU - Vineeta N. Pillai
AU - Farah Mustafa
AU - Tahir A. Rizvi
PY - 2026
DA - 2026/05/26
JO - Biological Reviews of the Cambridge Philosophical Society
DO - 10.1002/brv.70188
UR - https://doi.org/10.1002/brv.70188
AB - Retroviruses constitute a unique group of RNA viruses that have profoundly influenced both evolutionary trajectories and biomedical research. Their ability to reverse transcribe and integrate into host genomes has shaped genomic architecture across species and contributed to our understanding of oncogenes, gene regulation, and RNA biology. This review provides an in‐depth examination of retroviral molecular biology, beginning with the intricacies of their genome organization. We present an in‐depth discussion of the complex interplay of cis‐ and trans‐acting RNA elements during retrovirus replication, ending with a focus on genomic RNA packaging as the basis of infectious virion production. Emphasis is placed on how, among the various viral proteins, it is the retroviral Gag (Group‐specific antigen) that selectively orchestrates the packaging of the unspliced RNA amid a background of cellular and spliced viral RNAs. This is followed by our current understanding of how this process is affected by the retroviral Gag/Pol (Polymerase) and Gag/Pro (Protease)/Pol precursor proteins in the context to which the actual virion assembly takes place. Next, the review outlines emerging concepts regarding the structural basis of RNA recognition, the pivotal role of unpaired purines and long‐range intragenomic interactions (LRIs), in guiding genome selection. It discusses the dynamic processes of RNA dimerization and how it is not just intricately linked but is a pre‐requisite for genomic RNA encapsidation. Special attention is given to the new findings on transcription start site heterogeneity, cap sequestration, and epitranscriptomic modifications in shaping the fate of retroviral RNAs between translation and packaging since both these processes are critical for a successful viral life cycle. The review also addresses the involvement of assembly intermediates, and liquid–liquid phase separation in orchestrating efficient genome packaging and virus maturation. By integrating classical discoveries with recent findings, the review underscores the sophistication of retrovirus replication and proposes new avenues of research for therapeutic targeting of genome packaging and steps of viral assembly.
SN - 1464-7931
SN - 1469-185X
ER -