A highly structured nuclease-resistant, noncoding RNA produced by Flavoviruses is required for pathogenicity

G.P. Pijlman; A. Funk; N. Kondratieva; J.Y. Leung; L.M. van der Aa; W.J. Liu; A.C. Palmenberg; P.Y. Shi; A.A. Khromykh

doi:10.1016/j.chom.2008.10.007

A highly structured nuclease-resistant, noncoding RNA produced by Flavoviruses is required for pathogenicity

G.P. Pijlman, A. Funk, N. Kondratieva, J.Y. Leung, L.M. van der Aa, W.J. Liu, A.C. Palmenberg, P.Y. Shi, A.A. Khromykh

Research output: Contribution to journal › Article › Academic › peer-review

294 Citations (Scopus)

Abstract

Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.30.5 kb derived from the 3 untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3 untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.

Original language	English
Pages (from-to)	579-591
Journal	Cell Host & Microbe
Volume	4
Issue number	6
DOIs	https://doi.org/10.1016/j.chom.2008.10.007
Publication status	Published - 2008

Keywords

west-nile-virus
unfolded protein response
kunjin virus
secondary structure
encephalitis-virus
saccharomyces-cerevisiae
cyclization sequences
untranslated region
genetic algorithm
apoptotic pathway

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@article{c007d9053a0c44589cac9715a1f4dec3,

title = "A highly structured nuclease-resistant, noncoding RNA produced by Flavoviruses is required for pathogenicity",

abstract = "Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.30.5 kb derived from the 3 untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3 untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.",

keywords = "west-nile-virus, unfolded protein response, kunjin virus, secondary structure, encephalitis-virus, saccharomyces-cerevisiae, cyclization sequences, untranslated region, genetic algorithm, apoptotic pathway",

author = "G.P. Pijlman and A. Funk and N. Kondratieva and J.Y. Leung and {van der Aa}, L.M. and W.J. Liu and A.C. Palmenberg and P.Y. Shi and A.A. Khromykh",

year = "2008",

doi = "10.1016/j.chom.2008.10.007",

language = "English",

volume = "4",

pages = "579--591",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Elsevier",

number = "6",

}

A highly structured nuclease-resistant, noncoding RNA produced by Flavoviruses is required for pathogenicity. / Pijlman, G.P.; Funk, A.; Kondratieva, N.; Leung, J.Y.; van der Aa, L.M.; Liu, W.J.; Palmenberg, A.C.; Shi, P.Y.; Khromykh, A.A.

In: Cell Host & Microbe, Vol. 4, No. 6, 2008, p. 579-591.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - A highly structured nuclease-resistant, noncoding RNA produced by Flavoviruses is required for pathogenicity

AU - Pijlman, G.P.

AU - Funk, A.

AU - Kondratieva, N.

AU - Leung, J.Y.

AU - van der Aa, L.M.

AU - Liu, W.J.

AU - Palmenberg, A.C.

AU - Shi, P.Y.

AU - Khromykh, A.A.

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AB - Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.30.5 kb derived from the 3 untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3 untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.

KW - west-nile-virus

KW - unfolded protein response

KW - kunjin virus

KW - secondary structure

KW - encephalitis-virus

KW - saccharomyces-cerevisiae

KW - cyclization sequences

KW - untranslated region

KW - genetic algorithm

KW - apoptotic pathway

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DO - 10.1016/j.chom.2008.10.007

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JO - Cell Host & Microbe

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