Bunyamwera orthobunyavirus S-segment untranslated regions mediate poly(A) tail-independent translation.
The mRNAs of Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family, possess a 5' cap structure but lack a 3' poly(A) tail, a common feature of eukaryotic mRNAs that greatly enhances translation efficiency. Viral mRNAs also contain untranslated regions (UTRs) that flank the coding sequence. Using model virus-like mRNAs that harbor the Renilla luciferase reporter gene, we found that the 3' UTR of the BUNV small-segment mRNA mediated efficient translation in the absence of a poly(A) tail. Viral UTRs did not increase RNA stability, and polyadenylation did not significantly enhance reporter activity. Translation of virus-like mRNAs in transfected cells was unaffected by knockdown of poly(A)-binding protein (PABP) but was markedly reduced by depletion of eukaryotic initiation factor 4G, suggesting a PABP-independent process for translation initiation. In BUNV-infected cells, translation of polyadenylated but not virus-like mRNAs was inhibited. Furthermore, we demonstrate that the viral nucleocapsid protein binds to, and colocalizes with, PABP in the cytoplasm early in infection, followed by nuclear retention of PABP. Our results suggest that BUNV corrupts PABP function in order to inhibit translation of polyadenylated cellular mRNAs while its own mRNAs are translated in a PABP-independent process.
Blakqori
Gjon
G
Centre for Biomolecular Sciences, School of Biology, University of St. Andrews, North Haugh, St. Andrews KY16 9ST, Scotland, United Kingdom.
van Knippenberg
Ingeborg
I
Elliott
Richard M
RM
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D002042:Bunyamwera virus / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D006224:Cricetinae; D003593:Cytoplasm / Q000737:chemistry; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D019590:Nucleocapsid Proteins / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*
D020413:3' Untranslated Regions; D039603:Eukaryotic Initiation Factor-4G; D019590:Nucleocapsid Proteins; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D008156:Luciferases