Abstract
BackgroundG-quadruplexes are increasingly recognized as regulatory elements in human, animal, bacterial and plant genomes. The presence and function of G-quadruplexes are not well studied among herpesviruses; in particular, there are no systematic genome-wide analysis of these important secondary structures in herpesvirus genomes.ResultsWe performed genome-wide analysis of putative quadruplex sequences (PQS) in human herpesviruses. We found unusually high PQS densities among human herpesviruses. PQS are enriched in the repeat regions and regulatory regions of human herpesviruses. Interestingly, PQS densities are higher in regulatory regions of immediate early genes compared to early and late genes in most herpesviruses. In addition, the majority of genes functionally conserved across human herpesviruses contain one or more PQS within the regulatory regions. We also describe the existence of unique intramolecular PQS repeats or repetitive G-quadruplex motifs in herpesviruses. Functional studies confirm a role for G-quadruplexes in regulating the gene expression of human herpesviruses.ConclusionThe pervasiveness of PQS, their enrichment and conservation at specific genomic locations suggest that these structural entities may represent a novel class of functional elements in herpesviruses. Our findings provide the necessary framework for studies on the biological role of G-quadruplexes in herpesviruses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3282-1) contains supplementary material, which is available to authorized users.
Highlights
G-quadruplexes are increasingly recognized as regulatory elements in human, animal, bacterial and plant genomes
The randomization of sequences in using a sliding window approach reconfirmed that putative quadruplex sequences (PQS) densities in native full length sequences were higher for most herpesviruses compared to randomized sequences (Additional file 2: Figure S1a)
Herpesviruses are ubiquitous human pathogens and they often mimic regulatory elements of the host. In this systematic study of DNA G-quadruplexes in human herpesviruses we report several interesting findings on the presence and distribution of PQS at specific genomic locations including (a) The high PQS densities reported in our study for human herpesviruses are the highest reported for any genome studied in literature (b) Significant enrichment of PQS in the repeat regions and in the regulatory regions of human herpesviruses, suggesting a potential regulatory role for G-quadruplexes (c) The presence of PQS in the regulatory regions of the functionally conserved genes present across human herpesviruses (d) A potential role for PQS in the regulation of immediate early genes among most herpesviruses
Summary
G-quadruplexes are increasingly recognized as regulatory elements in human, animal, bacterial and plant genomes. The presence and function of G-quadruplexes are not well studied among herpesviruses; in particular, there are no systematic genome-wide analysis of these important secondary structures in herpesvirus genomes. G-quadruplexes are non-canonical nucleic acid secondary structures that are formed from G-rich sequences. These sequences consist of four stretches of G residues (each stretch with two or more G residues) interspersed by sequences of variable composition that form the loops. Given that G-quadruplexes are established transcriptional regulatory elements in human [3, 22, 23] it is possible that the simulation of structural DNA regulatory elements of the host by the virus may help complete the virus life cycle
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