title: Ebola Virus GP Gene Polyadenylation Versus RNA Editing.
abstract: Synthesis of Ebola virus (EBOV) surface glycoprotein (GP) is dependent on transcriptional RNA editing. Northern blot analysis of EBOV-infected cells using GP-gene-specific probes reveals that, in addition to full-length GP messenger RNAs (mRNAs), a shorter RNA is also synthesized, representing >40% of the total amount of GP mRNA. Sequence analysis demonstrates that this RNA is a truncated version of the full-length GP mRNA that is polyadenylated at the editing site and thus lacks a stop codon. An absence of detectable levels of protein synthesis in cellulo is consistent with the existence of tight regulation of the translation of such mRNA. However, nonstop GP mRNA was shown to be only slightly less stable than the same mRNA containing a stop codon, against the general belief in nonstop decay mechanisms aimed at detecting and destroying mRNAs lacking a stop codon. In conclusion, we demonstrate that the editing site indeed serves as a cryptic transcription termination/polyadenylation site, which rarely also functions to edit GP mRNA for expression of surface GP. This new data suggest that the downregulation of surface GP expression is even more dramatic than previously thought, reinforcing the importance of the GP gene editing site for EBOV replication and pathogenicity.
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM, U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Volchkova
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM, U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Vorac
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM, U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Repiquet-Paire
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM, U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM, U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France.
authors.forename: Viktor E
authors.initials: VE
authors.lastname: Volchkov
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D018388:Codon, Terminator / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D029043:Ebolavirus / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D026723:Polyadenylation / Q000235:genetics*; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D006023:Glycoproteins; D012333:RNA, Messenger; D014764:Viral Proteins
keywords: Ebola virus; GP gene; nonstop mRNA; polyadenylation; transcriptional RNA editing