Viral IRES Prediction System - a Web Server for Prediction of the IRES Secondary Structure In Silico

Hong, Jun-Jie; Wu, Tzong‐Yuan; Chang, Tsair-Yuan; Chen, Chung-Yung

doi:10.1371/journal.pone.0079288

Cited by 30 publications

(25 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The program failed to predict the presence of IRES in only two frog and two fish elements. The nature and position of the putative IRES was further examined by the VIPS server (Hong et al 2013), which search for structural similarity with known viral IRES. VIPS detected IRES in 31 long IGR including three of the four mammals (pig, elephant, and opossum).…”

Section: Resultsmentioning

confidence: 99%

“…Putative Internal Ribosome Entry Sites (IRES) were identified using the IRESPred tool, which uses 35 features based on sequence and structural properties to predict the presence of cellular or viral IRES (Kolekar et al 2016). We also used the Viral IRES Prediction System (VIPS), which uses the secondary structure of four groups of known viral IRES to predict putative viral IRES (Hong et al 2013). …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Evolution of Line-1 in Vertebrates

Boissinot

Sookdeo

2016

Genome Biol Evol

View full text Add to dashboard Cite

The abundance and diversity of the LINE-1 (L1) retrotransposon differ greatly among vertebrates. Mammalian genomes contain hundreds of thousands L1s that have accumulated since the origin of mammals. A single group of very similar elements is active at a time in mammals, thus a single lineage of active families has evolved in this group. In contrast, non-mammalian genomes (fish, amphibians, reptiles) harbor a large diversity of concurrently transposing families, which are all represented by very small number of recently inserted copies. Why the pattern of diversity and abundance of L1 is so different among vertebrates remains unknown. To address this issue, we performed a detailed analysis of the evolution of active L1 in 14 mammals and in 3 non-mammalian vertebrate model species. We examined the evolution of base composition and codon bias, the general structure, and the evolution of the different domains of L1 (5′UTR, ORF1, ORF2, 3′UTR). L1s differ substantially in length, base composition, and structure among vertebrates. The most variation is found in the 5′UTR, which is longer in amniotes, and in the ORF1, which tend to evolve faster in mammals. The highly divergent L1 families of lizard, frog, and fish share species-specific features suggesting that they are subjected to the same functional constraints imposed by their host. The relative conservation of the 5′UTR and ORF1 in non-mammalian vertebrates suggests that the repression of transposition by the host does not act in a sequence-specific manner and did not result in an arms race, as is observed in mammals.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Evolution of Line-1 in Vertebrates

Boissinot

Sookdeo

2016

Genome Biol Evol

View full text Add to dashboard Cite

show abstract

“…Computational analysis using the Viral IRES Prediction System (http://140.135.61.250/vips/) (39) indicated that the 5= UTR of RAN might possess intrinsic IRES (cap-independent) activity, which can escape virus-induced translation shutoff. The 5= UTR of RAN was inserted into a bicistronic reporter plasmid to study its IRES activity.…”

Section: Ran Is Necessary and Sufficient For Ev71 Replicationmentioning

confidence: 99%

Host MicroRNA miR-197 Plays a Negative Regulatory Role in the Enterovirus 71 Infectious Cycle by Targeting the RAN Protein

Tang

Huang

Chien

et al. 2016

J Virol

Self Cite

View full text Add to dashboard Cite

Enterovirus 71 (EV71), a member of Picornaviridae, is associated with severe central nervous system complications. In this study, we identified a cellular microRNA (miRNA), miR-197, whose expression was downregulated by viral infection in a timedependent manner. In miR-197 mimic-transfected cells, EV71 replication was inhibited, whereas the internal ribosome entry site (IRES) activity was decreased in EV71 strains with or without predicted miR-197 target sites, indicating that miR-197 targets host proteins to modulate viral replication. We thus used a quantitative proteomics approach, aided by the TargetScan algorithm, to identify putative target genes of miR-197. Among them, RAN was selected and validated as a genuine target in a 3= untranslated region (UTR) reporter assay. Reduced production of RAN by RNA interference markedly reduced the synthesis of EV71-encoded viral proteins and virus titers. Furthermore, reintroduction of nondegradable RAN into these knockdown cells rescued viral protein synthesis. miR-197 levels were modulated by EV71 to maintain RAN mRNA translatability at late times postinfection since we demonstrated that cap-independent translation exerted by its intrinsic IRES activity was occurring at times when translation attenuation was induced by EV71. EV71-induced downregulation of miR-197 expression increased the expression of RAN, which supported the nuclear transport of the essential viral proteins 3D/3CD and host protein hnRNP K for viral replication. Our data suggest that downregulation of cellular miRNAs may constitute a newly identified mechanism that sustains the expression of host proteins to facilitate viral replication. IMPORTANCEEnterovirus 71 (EV71) is a picornavirus with a positive-sense single-stranded RNA that globally inhibits the cellular translational system, mainly by cleaving cellular eukaryotic translation initiation factor 4G (eIF4G) and poly(A)-binding protein (PABP), which inhibits the association of the ribosome with the host capped mRNA. We used a microRNA (miRNA) microarray chip to identify the host miRNA 197 (miR-197) that was downregulated by EV71. We also used quantitative mass spectrometry and a target site prediction tool to identify the miR-197 target genes. During viral infection, the expression of the target protein RAN was upregulated considerably, and there was a parallel downregulation of miR-197. The nuclear transport of viral 3D/3CD protein and of the host proteins involved in viral replication proceeded in an RAN-dependent manner. We have identified a new mechanism in picornavirus through which EV71-induced cellular miRNA downregulation can regulate host protein levels to facilitate viral replication. M icroRNAs (miRNAs) are a group of endogenous, highly conserved noncoding single-stranded RNAs (ϳ22 nucleotides [nt] in length) that are transcribed from specialized genes and undergo series processing to generate final mature miRNAs. The human genome contains more than 2,580 distinct mature miRNA genes (http://www.mirbase.org/) (1), which act as...

show abstract

“…A primer design tool, PrimerHunter, for PCR-based virus subtype identification has also been constructed (104). In addition, there are various other resources that have been developed to address specific issues: (i) PhyloType, which uses parsimony to reconstruct ancestral traits and to select phylotypes (subsets of taxa and strains that share a history) (105); (ii) Geno2pheno, for estimating drug resistance and subtype prediction in HIV-1, HBV, and HCV (106); (iii) RotaC, an automated classification tool for group A rotaviruses (107); (iv) VirOligo, a database of virus-specific oligonucleotides (PCR primers and hybridization probes) as well as of experimental conditions for their usage (108); (v) Virus-PLoc, for predicting the subcellular localization of viral proteins within host cells and virus-infected cells (109); (vi) HIPdb and AVPdb, resources for antiviral peptides targeting HIV and 60 other medicinally important viruses, respectively (110,111); (vii) AVPpred, for prediction of highly effective antiviral peptides (112); (viii) VIPS, a viral internal ribosomal entry site (IRES) prediction system (113); and (ix) VaZyMolO, devoted to modular (pertaining to a structural or functional unit containing one or more protein domains) classification of viral proteins (114). Web-based tools to explore and analyze the structural aspects of viruses have also been established.…”

Section: Virus-host Interaction and Other Eclectic Softwaresmentioning

confidence: 99%

Unraveling the Web of Viroinformatics: Computational Tools and Databases in Virus Research

Sharma

Priyadarshini

Vrati

2015

J Virol

View full text Add to dashboard Cite

The beginning of the second century of research in the field of virology (the first virus was discovered in 1898) was marked by its amalgamation with bioinformatics, resulting in the birth of a new domain-viroinformatics. The availability of more than 100 Web servers and databases embracing all or specific viruses ( Viruses, known to have infected humankind since approximately the 15th century BC, are found in all cellular forms of life, from bacteria to chordates. Pathogenic human viruses are causative agents of many morbid diseases such as influenza, AIDS, dengue fever, encephalitis, hepatitis, diarrhea, and severe acute respiratory syndrome (SARS). However, despite the availability of effective vaccines and treatments for several diseases, ϳ6 million deaths occur every year due to viruses. Thus, it is imperative to develop remedies against these viral invaders. Advances in molecular biology and bioinformatics have resulted in a deluge of genomic and experimental data. To store, examine, and disseminate all this information, 112 viroinformatics resources have been developed (as of May 2014; Table 1). The International Committee on Taxonomy of Viruses (ICTV) that performs the task of naming and classifying viruses lists 2,618 species. Strikingly, the genomes of ϳ40,000 viral strains, across more than 900 species, have been sequenced (NCBI Viral Genome Resource, NCBI Influenza Virus Resource [NCBI-IVR], and http://www .viprbrc.org/).The aims of this article are manyfold. The first aim is to provide an extensive list of viroinformatics resources. At present, the information about these resources is so disparate that it is almost impossible to be aware of all the tools (many of which have been developed recently). The second aim is to categorize the resources based on their specificity for a particular virus, application, or task. The third aim is to compare tools performing similar tasks on the basis of (i) importance, popularity, and reliability (reflected by the citation index of a tool), (ii) the number of genomes and sequences included, (iii) the unique features of a given resource, and (iv) ease of use (whether a Web interface is available). If available, references to publications comparing similar tools have also been provided. The fourth aim is to provide information about tools that have been succeeded by a newer resource, have not been updated for more than past 2 years, or are currently inaccessible. The fifth (and most important) aim is to enable virologists to get an overview of tools capable of carrying out a desired task and select the most suitable one(s). For compiling the comprehensive index of resources presented here, an initial list was first prepared by extensively searching the literature (PubMed [http://www.ncbi.nlm.nih.gov/pubmed] and ScienceDirect [http://www.sciencedirect.com]) using all possible combinations of various keywords. Subsequently, all the publications describing these tools were thoroughly explored to find other resources mentioned in them. This greatly expanded the initia...

show abstract

Viral IRES Prediction System - a Web Server for Prediction of the IRES Secondary Structure In Silico

Cited by 30 publications

References 30 publications

The Evolution of Line-1 in Vertebrates

The Evolution of Line-1 in Vertebrates

Host MicroRNA miR-197 Plays a Negative Regulatory Role in the Enterovirus 71 Infectious Cycle by Targeting the RAN Protein

Unraveling the Web of Viroinformatics: Computational Tools and Databases in Virus Research

Contact Info

Product

Resources

About