title: Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus.
abstract: The impact of RNA viruses on the posttranscriptional regulation of cellular gene expression is unclear. Sindbis virus causes a dramatic relocalization of the cellular HuR protein from the nucleus to the cytoplasm in infected cells. This is to the result of the expression of large amounts of viral RNAs that contain high-affinity HuR binding sites in their 3' UTRs effectively serving as a sponge for the HuR protein. Sequestration of HuR by Sindbis virus is associated with destabilization of cellular mRNAs that normally bind HuR and rely on it to regulate their expression. Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus. These studies suggest a molecular mechanism of virus-host interaction that probably has a significant impact on virus replication, cytopathology, and pathogenesis.
authors.affiliation: Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80525, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Barnhart
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Moon
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Emch
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Wilusz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilusz
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D006224:Cricetinae; D003593:Cytoplasm / Q000235:genetics; D051959:ELAV Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D026723:Polyadenylation / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry*; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics*; D012845:Sindbis Virus / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D012333:RNA, Messenger; D012367:RNA, Viral