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 in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (49), p.19294-19299
Main Authors: Mir, M.A, Duran, W.A, Hjelle, B.L, Ye, C, Panganiban, A.T
Format: Article
Language:English
Subjects:
Antibodies
Binding sites
Biological Sciences
Cells
Codon, Nonsense - genetics
Cytoplasm - virology
Cytoplasmic Granules - virology
Gene Expression Regulation, Viral
Green Fluorescent Proteins - genetics
Hantavirus
Hantavirus - genetics
Hantavirus - growth & development
Hantavirus Infections - virology
HeLa Cells
Humans
Messenger RNA
Nucleocapsid Proteins - genetics
Nucleotides
Plasmids
Polymerase chain reaction
Protein Biosynthesis
Proteins
Ribonucleic acid
RNA
RNA stability
RNA Stability - physiology
RNA, Messenger - genetics
Transcription, Genetic
Viruses
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0807211105