Storage of cellular 5' mRNA caps in P bodies for viral cap-snatching.
The minus strand and ambisense segmented RNA viruses include multiple important human pathogens and are divided into three families, the Orthomyxoviridae, the Bunyaviridae, and the Arenaviridae. These viruses all initiate viral transcription through the process of "cap-snatching," which involves the acquisition of capped 5' oligonucleotides from cellular mRNA. Hantaviruses are emerging pathogenic viruses of the Bunyaviridae family that replicate in the cytoplasm of infected cells. Cellular mRNAs can be actively translated in polysomes or physically sequestered in cytoplasmic processing bodies (P bodies) where they are degraded or stored for subsequent translation. Here we show that the hantavirus nucleocapsid protein binds with high affinity to the 5' cap of cellular mRNAs, protecting the 5' cap from degradation. We also show that the hantavirus nucleocapsid protein accumulates in P bodies, where it sequesters protected 5' caps. P bodies then serve as a pool of primers during the initiation of viral mRNA synthesis by the viral polymerase. We propose that minus strand segmented viruses replicating in the cytoplasm have co-opted the normal degradation machinery of P bodies for storage of cellular caps. Our data also indicate that modification of the cap-snatching model is warranted to include a role for the nucleocapsid protein in cap acquisition and storage.
Mir
M A
MA
Department of Molecular Genetics, Cancer Research Facility University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Duran
W A
WA
Hjelle
B L
BL
Ye
C
C
Panganiban
A T
AT
D018389:Codon, Nonsense / Q000235:genetics; D003593:Cytoplasm / Q000821:virology; D003594:Cytoplasmic Granules / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D049452:Green Fluorescent Proteins / Q000235:genetics; D006476:Orthohantavirus / Q000235:genetics* / Q000254:growth & development*; D018778:Hantavirus Infections / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D019590:Nucleocapsid Proteins / Q000235:genetics; D014176:Protein Biosynthesis; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D018389:Codon, Nonsense; D019590:Nucleocapsid Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins