Genomic RNA folding mediates assembly of human parechovirus

TY - JOUR

T1 - Genomic RNA folding mediates assembly of human parechovirus

AU - Twarock, Reidun

AU - Dykeman, Eric Charles

AU - Shakeel, Shabih

AU - White, Simon

AU - Ora, Ari

AU - Cockburn, Joseph

AU - Butcher, Sarah

AU - Stockley, Peter

N1 - © 2017, The Authors.

PY - 2017/2/23

Y1 - 2017/2/23

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - Base Pairing

KW - Binding Sites

KW - Capsid Proteins/genetics

KW - Computational Biology

KW - Conserved Sequence

KW - Gene Expression

KW - Genome, Viral

KW - Humans

KW - Models, Molecular

KW - Parechovirus/genetics

KW - Protein Binding

KW - RNA Folding

KW - RNA, Viral/genetics

KW - Reverse Genetics

KW - SELEX Aptamer Technique

KW - Virion/genetics

KW - Virus Assembly

UR - http://www.scopus.com/inward/record.url?scp=85013793619&partnerID=8YFLogxK

U2 - 10.1038/s41467-016-0011-z

DO - 10.1038/s41467-016-0011-z

M3 - Article

C2 - 28232749

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 5

ER -