title: Genomic RNA folding mediates assembly of human parechovirus.
abstract: Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets.The mechanism underlying packaging of genomic RNA into viral particles is not well understood for human parechoviruses. Here the authors identify short RNA motifs in the parechovirus genome that bind capsid proteins, providing approximately 60 specific interactions for virion assembly.
authors.affiliation: Institute of Biotechnology and Department of Biosciences, University of Helsinki, Helsinki, 00790, Finland.
authors.forename: Shabih
authors.identifier: http://orcid.org/0000-0003-3651-6087
authors.initials: S
authors.lastname: Shakeel
authors.affiliation: Departments of Mathematics and Biology and York Centre for Complex Systems Analysis, University of York, York, YO10 5DD, UK.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Dykeman
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: White
authors.affiliation: Institute of Biotechnology and Department of Biosciences, University of Helsinki, Helsinki, 00790, Finland.|Department of Applied Physics and Department of Biotechnology and Chemical Technology, Aalto University, Espoo, 02150, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Ora
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Joseph J B
authors.initials: JJB
authors.lastname: Cockburn
authors.affiliation: Institute of Biotechnology and Department of Biosciences, University of Helsinki, Helsinki, 00790, Finland. sarah.butcher@helsinki.fi.
authors.forename: Sarah J
authors.identifier: http://orcid.org/0000-0001-7060-5871
authors.initials: SJ
authors.lastname: Butcher
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. p.g.stockley@leeds.ac.uk.
authors.forename: Peter G
authors.identifier: http://orcid.org/0000-0002-1360-2751
authors.initials: PG
authors.lastname: Stockley
authors.affiliation: Departments of Mathematics and Biology and York Centre for Complex Systems Analysis, University of York, York, YO10 5DD, UK. reidun.twarock@york.ac.uk.
authors.forename: Reidun
authors.initials: R
authors.lastname: Twarock
mesh_terms: D020816:Amino Acid Motifs; D020029:Base Pairing; D001665:Binding Sites; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D019295:Computational Biology; D017124:Conserved Sequence; D015870:Gene Expression; D016679:Genome, Viral; D006801:Humans; D008958:Models, Molecular; D030061:Parechovirus / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D059370:RNA Folding; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D059386:Reverse Genetics; D052156:SELEX Aptamer Technique; D014771:Virion / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral