Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family

Fleming, Aaron M.; Ding, Yun; Alenko, Anton; Burrows, Cynthia J.

doi:10.1021/acsinfecdis.6b00109

Cited by 127 publications

(142 citation statements)

References 37 publications

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“…m 6 A) (Lichinchi et al, 2016) in host cells. In addition, computational analyses suggest that the ZIKV genomic RNA possesses conserved G-Quadruplexes (Fleming et al, 2016) as well as the capacity to generate a large number of sfRNAs and sRNAs (Akiyama et al, 2016). Whether any of these mechanisms contribute to ZIKV replication and host cell pathogenesis remains to be functionally determined.…”

Section: Opportunities and Challenges For Zikv Research Using Stem Cellsmentioning

confidence: 99%

Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities

2016

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SummaryThe re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborn and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues and animal models. These efforts provided significant insight into cellular targets, pathogenesis and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing. Here we review the remarkable progress in stem cell-based ZIKV research and discuss current challenges and future opportunities.

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Section: Opportunities and Challenges For Zikv Research Using Stem Cellsmentioning

confidence: 99%

Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities

2016

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“…Such G4 forming sequences have been reported to be prevalent in genomes, such as immunoglobulin switch regions and promoter regions of oncogenes and telomere ends 4, 5 , as well as in particular RNA domains, such as the first introns, 5′- and 3′- untranslated regions, telomeric RNA 6 , and the genomic RNA of Zika virus replication 7 . Accumulating evidence has suggested that G4s play an intrinsic role in gene expression 8–14 .…”

Section: Introductionmentioning

confidence: 99%

Development of squaraine based G-quadruplex ligands using click chemistry

Zhang

Wei

Bing

et al. 2017

Sci Rep

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The G-quadruplex (G4) structures of nucleic acids are considered to play an intrinsic role in gene expression. To this end, the development of new G4 ligands has attracted extensive research interests towards potential applications as G4-targeted drugs and molecular probes. To date, the majority of G4 ligands have been composed of an extended planar aromatic scaffold that interacts with the terminal G-tetrad plane via π-π interactions, and various side chains that interact with the sugar-phosphate backbone, loops or grooves of the G4 structures. The side chains act to modulate the affinity and selectivity of the G4 ligands, alongside influencing their biodistribution. Here, we present a click chemistry methodology to generate a series of squaraine-based G4 ligand derivatives based on our previously reported G4 probe (named CSTS) but with varing side chains. We find that importantly these new G4 ligand derivatives retain the G4 selectivity, optical properties and low cytotoxicity of CSTS, but exhibit different binding behaviors to G4 structures, and distinct cellular uptake efficiencies. Indeed, of these new complexes, several exhibit much higher affinity and cellular uptake than CSTS. Overall, this novel, facile and highly effective strategy has significant future potential for the high-throughput screening of G4 ligands or probes targeted towards in vivo applications.

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“…G4s have been reported in the SARS coronavirus7, the human papilloma, hepatitis C, Zika and Ebola virus genomes891011. Among herpesviruses, RNA G4s have been implicated in the regulation of DNA replication and translation of the Epstein–Barr virus1213.…”

mentioning

confidence: 99%

The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes

Scalabrin

Frasson

Ruggiero

et al. 2017

Sci Rep

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G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells.

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Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family

Cited by 127 publications

References 37 publications

Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities

Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities

Development of squaraine based G-quadruplex ligands using click chemistry

The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes

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