The function of DNA binding protein nucleophosmin in AAV replication

Satkunanathan, Stifani; Thorpe, Robin; Zhao, Yuan

doi:10.1016/j.virol.2017.07.007

Cited by 20 publications

(14 citation statements)

References 54 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study reported the presence of G4s in the AAV genome. The DNA binding protein nucleophosmin (NPM1), which is known to enhance AAV infectivity, directly interacts with G4s: 18 putative G4s were identified, located within the inverted terminal repeat region ( 86 ).…”

Section: G-quadruplexes In Viruses: Presence and Functionmentioning

confidence: 99%

G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

Ruggiero

Richter

2018

Nucleic Acids Research

357

307

View full text Add to dashboard Cite

G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed.

show abstract

Section: G-quadruplexes In Viruses: Presence and Functionmentioning

confidence: 99%

G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

Ruggiero

Richter

2018

Nucleic Acids Research

357

307

View full text Add to dashboard Cite

show abstract

“…In RNA viruses, such as retroviruses, flaviviruses, and filoviruses, G4s present in the long terminal repeat (LTR), in the UTR, or in the coding region modulate gene expression and recombination [ 31 – 38 ]. In DNA viruses, G4s present in the genomes of adeno-associated virus and human herpesviruses regulate viral DNA replication [ 39 – 43 ], while G4s in the promoter region of hepatitis B virus (HBV) and in the mRNA of Epstein-Barr virus modulate transcription and translation [ 44 ] [ 45 , 46 ]. However, most of these studies aimed to understand the role of individual viral G4s, while genome-wide studies using the entire viral genomes are limited.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of regulatory G-quadruplexes affecting gene expression in human cytomegalovirus

et al. 2018

View full text Add to dashboard Cite

G-quadruplex (G4), formed by repetitive guanosine-rich sequences, is known to play various key regulatory roles in cells. Herpesviruses containing a large double-stranded DNA genome show relatively higher density of G4-forming sequences in their genomes compared to human and mouse. However, it remains poorly understood whether all of these sequences form G4 and how they play a role in the virus life cycle. In this study, we performed genome-wide analyses of G4s present in the putative promoter or gene regulatory regions of a 235-kb human cytomegalovirus (HCMV) genome and investigated their roles in viral gene expression. We evaluated 36 putative G4-forming sequences associated with 20 genes for their ability to form G4 and for the stability of G4s in the presence or absence of G4-stabilizing ligands, by circular dichroism and melting temperature analyses. Most identified sequences formed a stable G4; 28 sequences formed parallel G4s, one formed an antiparallel G4, and four showed mixed conformations. However, when we assessed the effect of G4 on viral promoters by cloning the 20 putative viral promoter regions containing 36 G4-forming sequences into the luciferase reporter and monitoring the expression of luciferase reporter gene in the presence of G4-stabilizing chemicals, we found that only 9 genes were affected by G4 formation. These results revealed promoter context-dependent gene suppression by G4 formation. Mutational analysis of two potential regulatory G4s also demonstrated gene suppression by the sequence-specific G4 formation. Furthermore, the analysis of a mutant virus incapable of G4 formation in the UL35 promoter confirmed promoter regulation by G4 in the context of virus infection. Our analyses provide a platform for assessing G4 functions at the genomic level and demonstrate the properties of the HCMV G4s and their regulatory roles in viral gene expression.

show abstract

“…In the dsDNA group, G4s were described in both Herpesviridae and Papillomaviridae families [12][13][14][15][16][17][18][19][20]. In ssDNA viruses, the presence of G4s was reported in the adeno-associated virus genome [21]. RNA G4s were described in the genomes of both ssRNA (+) (i.e.…”

mentioning

confidence: 99%

G-quadruplex forming sequences in the genome of all known human viruses: A comprehensive guide

et al. 2018

View full text Add to dashboard Cite

G-quadruplexes are non-canonical nucleic-acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of potential quadruplex-forming sequences (PQS) in the genome of all known viruses that can infect humans. We show that occurrence and location of PQSs are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the PQS classification. For each virus we provide: i) the list of all PQS present in the genome (positive and negative strands), ii) their position in the viral genome, iii) the degree of conservation among strains of each PQS in its genome context, iv) the statistical significance of PQS abundance. This information is accessible from a database to allow the easy navigation of the results: http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=g4virus. The availability of these data will greatly expedite research on G-quadruplex in viruses, with the possibility to accelerate finding therapeutic opportunities to numerous and some fearsome human diseases.

show abstract

The function of DNA binding protein nucleophosmin in AAV replication

Cited by 20 publications

References 54 publications

G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy

Genome-wide analysis of regulatory G-quadruplexes affecting gene expression in human cytomegalovirus

G-quadruplex forming sequences in the genome of all known human viruses: A comprehensive guide

Contact Info

Product

Resources

About