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

Abstract

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 putative G-quadruplexes in the genome of all known viruses that can infect humans. We show that the presence, distribution, and location of G-quadruplexes 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 G-quadruplex classification. For each virus we provide: i) the list of all G-quadruplexes formed by GG-, GGG-and GGGG-islands present in the genome (positive and negative strands), ii) their position in the viral genome along with the known function of that region, iii) the degree of conservation among strains of each G-quadruplex in its genome context, iv) the statistical significance of G-quadruplex formation. This information is accessible from a database

Integrative analysis reveals RNA G-Quadruplexes in UTRs are selectively constrained and enriched for functional associations

“…In both K562 and HepG2 cells, we observe similar enrichment for GRSF1 binding over 5' and 3' UTR pG4 sequences, leading us to speculate that a similar mechanism may exist to melt pG4 sequences, and promote degradation of their parent RNA transcripts in human cells. reported in the literature 36 , and G4-forming sequences have been found to occur commonly in multiple viral genomes 37 . This, coupled with the observation that RNA G4s appear to be universally depleted within prokaryotic transcriptomes 12 , makes it tempting to speculate that viruses may have evolved G4 sequences specifically as a mechanism for co-opting host cell machinery involved in gene expression and RNA regulation.…”

In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and OtherNidoviralesSuggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

“…Local DNA structures have been shown to play important roles in basic biological processes, including replication and transcription Travers and Muskhelishvili, 2015;Surovtsev and Jacobs-Wagner, 2018). PQS analyses of human viruses have clearly demonstrated that these sequences are conserved also in the viral genomes (Lavezzo et al, 2018) and could be targets for antiviral therapies (Wang et al, 2015;Krafčíková et al, 2017;Ruggiero and Richter, 2018). For example, the conserved PQS sequence present in the L gene of Zaire ebolavirus and related to its replication is inhibited by interaction with G-quadruplex ligand TMPyP4, and this finding has led to suggestions that G-quadruplex RNA stabilization could constitute a new strategy against Ebola virus disease (Wang et al, 2016).…”

“…These have been detected in various This is a provisional file, not the final typeset article genomes, but most extensively they have been described in human genomes (Chambers et al, 2015;Bedrat et al, 2016;Hänsel-Hertsch et al, 2016). They are present also in viruses (Lavezzo et al, 2018;Frasson et al, 2019). G-quadruplexes probably play an important role in regulating replication in most viral nucleic acids (Lavezzo et al, 2018), and these structures have been suggested as targets for antiviral therapy (Métifiot et al, 2014;Ruggiero and Richter, 2018).…”

“…They are present also in viruses (Lavezzo et al, 2018;Frasson et al, 2019). G-quadruplexes probably play an important role in regulating replication in most viral nucleic acids (Lavezzo et al, 2018), and these structures have been suggested as targets for antiviral therapy (Métifiot et al, 2014;Ruggiero and Richter, 2018). Along with cruciforms and hairpins, which can be formed in nucleic acids by inverted repeats (IRs), G-quadruplexes are significant genome elements playing specific biological roles.…”

“…In all prokaryotic and eukaryotic cells, as well as viruses, there have been found sequence motifs such as IR sequences forming cruciforms and hairpins or G-rich sequences that form G-quadruplexes Lavezzo et al, 2018;Bartas et al, 2019). In the present research, we conducted a systematic and comprehensive bioinformatic study searching for the occurrence of IRs and putative quadruplex sites (PQSs) within the genomes of all known Nidovirales.…”