Epitranscriptomic regulation of HIV-1 full-length RNA packaging

Pereira-Montecinos, Camila; Toro-Ascuy, Daniela; Ananías-Sáez, Catarina; Gaete-Argel, Aracelly; Rojas-Fuentes, Cecilia; Riquelme-Barrios, Sebastián; Rojas-Araya, Bárbara; García-de-Gracia, Francisco; Aguilera-Cortés, Paulina; Chnaiderman, Jonás; Acevedo, Mónica L.; Valiente-Echeverría, Fernando; Soto-Rifo, Ricardo

doi:10.1093/nar/gkac062

Cited by 27 publications

(50 citation statements)

References 62 publications

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“…Several different laboratories have observed that the retroviral Gag proteins of HIV-1, RSV, MMTV, MLV, FIV, PFV, and MPMV undergo nuclear localization (9–23, 25, 26, 100–103). As described in detail in this report, six previously published proteomic studies searching for binding partners of HIV-1 Gag identified many nuclear proteins (30–35).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, we identified two components of the WMM complex, CBLL1 (Cbl Pro-to-Oncogene Like 1; present in RSV and HIV-1 datasets) and WTAP (Wilms tumor 1 associated protein; RSV dataset only), which mediates m6-methyladenosine (m6A) methylation of RNAs. This RNA modification affects RNA splicing and processing, and full length HIV-1 RNA containing m6A has displayed a bias towards serving as template RNA for the translation of viral proteins, as opposed to being packaged as gRNA (103). Interaction with components of the WMM complex could simply serve to localize Gag to sites where viral RNA may exist, but it is intriguing to consider the possibility that Gag antagonizes the function of this complex to maintain a pool of genomic RNA.…”

Section: Discussionmentioning

confidence: 99%

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Comparative analysis of retroviral Gag-host cell interactions: focus on the nuclear interactome

Lambert,

Rice,

Maldonado

et al. 2024

Preprint

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Retroviruses exploit a variety of host proteins to assemble and release virions from in-fected cells. To date, most studies that examined possible interacting partners of retroviral Gag proteins focused on host proteins that localize primarily to the cytoplasm or plasma membrane. Given the recent findings that several full-length Gag proteins localize to the nucleus, identifying the Gag-nuclear interactome has high potential for novel findings that reveal previously un-known host processes. In this study, we systematically compared nuclear factors identified in published HIV-1 proteomic studies which had used a variety of experimental approaches. In addition, to contribute to this body of knowledge, we report results from a mass spectrometry approach using affinity-tagged (His6) HIV-1 and RSV Gag proteins mixed with nuclear extracts. Taken together, the previous studies, as well as our own, identified potential binding partners of HIV-1 and RSV Gag involved in several nuclear processes, including transcription, splicing, RNA modification, and chromatin remodeling. Although a subset of host proteins interacted with both Gag proteins, there were also unique host proteins belonging to each interactome dataset. To validate one of the novel findings, we demonstrated the interaction of RSV Gag with a member of the Mediator complex, Med26, which is required for RNA polymerase II-mediated transcription. These results provide a strong premise for future functional studies to investigate roles for these nuclear host factors that may have shared functions in the biology of both retroviruses, as well as functions specific to RSV and HIV-1, given their distinctive hosts and molecular pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative analysis of retroviral Gag-host cell interactions: focus on the nuclear interactome

Lambert,

Rice,

Maldonado

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In the intracellular environment, the interaction between Gag and gRNA may be regulated by many different mechanisms ( Ding et al 2021 ; Pereira-Montecinos et al 2022 ). For example, a series of reports showed that the fate of HIV-1 RNA transcripts depends on alternative transcription start sites ( Masuda et al 2015 ; Kharytonchyk et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Distinct Gag interaction properties of HIV-1 RNA 5′ leader conformers reveal a mechanism for dimeric genome selection

Yang

Liu

Cui

et al. 2022

RNA

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During HIV-1 assembly, two copies of viral genomic RNAs (gRNA) are selectively packaged into new viral particles. This process is mediated by specific interactions between HIV-1 Gag and the packaging signals at 5′ RNA leader (5′L). 5′L is able to adopt different conformations, which promotes either gRNA dimerization and packaging or Gag translation. Dimerization and packaging are coupled. Whether the selective packaging of gRNA dimer is due to favorable interactions between Gag and 5′L in packaging conformation is not known. Here, using RNAs mimicking the two 5′L conformers, we show that 5′L conformation dramatically affects Gag-RNA interactions. Compare to the RNA in translation conformation (5′LT), the one in packaging conformation (5′LP) is able to bind more Gag molecules. Gag associates with 5′LPfaster than it binds to 5′LT; Gag dissociates from 5′LPmuch slower. The Gag-5′LPcomplex is more stable at high salt. The NC-SP2-p6 region of Gag likely accounts for the faster association and slower dissociation kinetics for the Gag-5′LPinteraction and for the higher stability.In summary, our data suggests that conformational changes play an important role in the selection of dimeric genomes, probably by affecting the dissociation kinetics and stability of the Gag-5′L complex.

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“…A very recent study suggested that N 6 ‐methyladenosine deposition could play a role in regulating transcription versus packaging functions of individual HIV‐1 RNA transcripts. [ 98 ] Although this mechanism is at odds with evidence that translation and packaging are mediated by different transcripts, the proposed role for epitranscriptomic regulation of HIV‐1 RNA function is intriguing and deserves further exploration.…”

Section: Cap Sequestration Is Required For Hiv‐1 Rna Packagingmentioning

confidence: 99%

Sequestering the 5′‐cap for viral RNA packaging

Ding

Summers

2022

BioEssays

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Many viruses evolved mechanisms for capping the 5′-ends of their plus-strand RNAs as a means of hijacking the eukaryotic messenger RNA (mRNA) splicing/translation machinery. Although capping is critical for replication, the RNAs of these viruses have other essential functions including their requirement to be packaged as either genomes or pre-genomes into progeny viruses. Recent studies indicate that human immunodeficiency virus type-1 (HIV-1) RNAs are segregated between splicing/translation and packaging functions by a mechanism that involves structural sequestration of the 5′-cap. Here, we examined studies reported for other viruses and retrotransposons that require both selective packaging of their RNAs and 5′-RNA capping for host-mediated translation. Our findings suggest that viruses and retrotransposons have evolved multiple mechanisms to control 5′-cap accessibility, consistent with the hypothesis that removal or sequestration of the 5′ cap enables packageable RNAs to avoid capture by the cellular RNA processing and translation machinery.

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Epitranscriptomic regulation of HIV-1 full-length RNA packaging

Cited by 27 publications

References 62 publications

Comparative analysis of retroviral Gag-host cell interactions: focus on the nuclear interactome

Comparative analysis of retroviral Gag-host cell interactions: focus on the nuclear interactome

Distinct Gag interaction properties of HIV-1 RNA 5′ leader conformers reveal a mechanism for dimeric genome selection

Sequestering the 5′‐cap for viral RNA packaging

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