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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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 49; pp. 19294 - 19299
Main Authors:	Mir, M.A, Duran, W.A, Hjelle, B.L, Ye, C, Panganiban, A.T
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 09-12-2008 National Acad Sciences
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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: M.A.M. and A.T.P. designed research; M.A.M. and W.A.D. performed research; M.A.M., B.L.H., and C.Y. contributed new reagents/analytic tools; M.A.M. and A.T.P. analyzed data; and M.A.M. and A.T.P. wrote the paper. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved October 3, 2008
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0807211105