Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome
Open accessAbstract
Significance Current dogma states that the integrated HIV type 1 provirus encodes a single RNA transcript that serves as both mRNA for generating viral proteins and as genomic RNA that is packaged and used for reverse transcription. We now show that multiple transcripts with different functions are generated in infected cells, a consequence of heterogeneous transcriptional start site usage. Transcripts that begin with a single capped guanosine are specifically selected for packaging, whereas those that begin with two or three capped guanosines are enriched on polysomes and used for translation. In vitro studies with recombinant 5′-leader transcripts reveal a mechanism by which the incorporation of a single 5′ guanosine dramatically alters the structure, function, and fate of the viral RNA.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HIV-1 generates multiple unspliced RNA species (e.g. 1 G versus 3 G RNAs) that differ only slightly at the 5′ end, but fold into distinct structures with differing packaging efficiencies.
“HIV-1 generates multiple unspliced RNA species (e.g. 1 G versus 3 G RNAs) that differ only slightly at the 5′ end, but fold into distinct structures with differing packaging efficiencies.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Kharytonchyk et al. 2016
The 1 G RNA preferentially adopts conformations that leave the DIS and Gag-binding motifs such as unpaired purines fully exposed thus favoring gRNA packaging.
“The 1 G RNA preferentially adopts conformations that leave the DIS and Gag-binding motifs such as unpaired purines fully exposed thus favoring gRNA packaging.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Kharytonchyk et al. 2016
The 3 G RNA adopts a different conformation in which DIS and Gag binding sites are obscured, rendering it more disposed to translation than to packaging.
“On the other hand, the 3 G RNA adopts a different conformation in which DIS and Gag binding sites are obscured, rendering it more disposed to translation than to packaging”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Kharytonchyk et al. 2016
Cites
Genome-wide analysis of mammalian promoter architecture and evolution
Carninci, P., Sandelin, A., Lenhard, B., Katayama, S., Shimokawa, K., Ponjavic, J., Semple, C. A. M., Taylor, M. S., Engström, P. G., Frith, M. C., et al. (2006) · Nature Genetics · doi:10.1038/ng1789 · Cited by 1,350 · see citing works
How retroviruses select their genomes
D'Souza, V., & Summers, M. F. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1210 · Cited by 339 · see citing works
Self-citationDimeric RNA Recognition Regulates HIV-1 Genome Packaging
Nikolaitchik, O. A., Dilley, K. A., Fu, W., Gorelick, R. J., Tai, S.-H. S., Soheilian, F., Ptak, R. G., Nagashima, K., Pathak, V. K., & Hu, W.-S. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003249 · Cited by 106 · see citing works
Lever, A. M. L. (2007) · Advances in Pharmacology · doi:10.1016/s1054-3589(07)55001-5 · Cited by 103 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Direct translation of incoming retroviral genomes
Köppke, J., Keller, L.-E., Stuck, M., Arnow, N. D., Bannert, N., Doellinger, J., & Cingöz, O. (2024) · Nature Communications · doi:10.1038/s41467-023-44501-7 · Cited by 10 · see citing works
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“On the other hand, the 3 G RNA adopts a different conformation in which DIS and Gag binding sites are obscured, rendering it more disposed to translation than to packaging (Masuda et al. 2015 , Kharytonchyk et al. 2016 , Brown et al. 2020 , Ding et al. 2021 , Nikolaitchik et al. 2023 ).”
- Authors
- Kharytonchyk, S., Monti, S., Smaldino, P. J., Van, V., Bolden, N. C., Brown, J. D., Russo, E., Swanson, C., Shuey, A., Telesnitsky, A., & Summers, M. F.
- Affiliations
- University of Michigan (US)
- University of Maryland, Baltimore County (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Summers, Michael F.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-11-09
- Volume
- 113
- Issue
- 47
- Pages
- 13378-13383
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5127319
- OpenAlex
- W2555494550
- Cited by
- 123
- References
- 4
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 8 · 2022: 14 · 2021: 25 · 2020: 16 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 1
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of General Medical Sciences (GM42561, P50 GM103297, R25 GM055036)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- 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
- Keywords
- HIV-1, HIV-1 provirus, viral RNA packaging, polysome association, viral RNA translation, RNA structure, multiple transcripts, reverse transcription
- MeSH terms
- Guanosine, Mutation, Polyribosomes, Promoter Regions, Genetic, RNA, Viral, Transcription, Genetic, Virus Replication, Molecular Structure, HIV-1, Genome, Viral, Genetic Heterogeneity, Virus Assembly, Transcription Initiation Site
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
