title: Picornavirus modification of a host mRNA decay protein.
abstract: Due to the limited coding capacity of picornavirus genomic RNAs, host RNA binding proteins play essential roles during viral translation and RNA replication. Here we describe experiments suggesting that AUF1, a host RNA binding protein involved in mRNA decay, plays a role in the infectious cycle of picornaviruses such as poliovirus and human rhinovirus. We observed cleavage of AUF1 during poliovirus or human rhinovirus infection, as well as interaction of this protein with the 5' noncoding regions of these viral genomes. Additionally, the picornavirus proteinase 3CD, encoded by poliovirus or human rhinovirus genomic RNAs, was shown to cleave all four isoforms of recombinant AUF1 at a specific N-terminal site in vitro. Finally, endogenous AUF1 was found to relocalize from the nucleus to the cytoplasm in poliovirus-infected HeLa cells to sites adjacent to (but distinct from) putative viral RNA replication complexes.
  
  
  OBJECTIVE
  This study derives its significance from reporting how picornaviruses like poliovirus and human rhinovirus proteolytically cleave a key player (AUF1) in host mRNA decay pathways during viral infection. Beyond cleavage of AUF1 by the major viral proteinase encoded in picornavirus genomes, infection by poliovirus results in the relocalization of this host cell RNA binding protein from the nucleus to the cytoplasm. The alteration of both the physical state of AUF1 and its cellular location illuminates how small RNA viruses manipulate the activities of host cell RNA binding proteins to ensure a faithful intracellular replication cycle.
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Rozovics
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Chase
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cathcart
authors.forename: Wayne
authors.initials: W
authors.lastname: Chou
authors.forename: Paul D
authors.initials: PD
authors.lastname: Gershon
authors.forename: Saiprasad
authors.initials: S
authors.lastname: Palusa
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilusz
authors.forename: Bert L
authors.initials: BL
authors.lastname: Semler
mesh_terms: D000086042:3C Viral Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D017955:Poliovirus / Q000502:physiology*; D059748:Proteolysis; D012367:RNA, Viral / Q000378:metabolism*; D012229:Rhinovirus / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012367:RNA, Viral; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases