A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

Kuo Feng Weng, Chuan Tien Hung, Po Ting Hsieh, Mei Ling Li, Guang Wu Chen, Yu An Kung, Peng Nien Huang, Rei Lin Kuo, Li Lien Chen, Jing Yi Lin, Robert Y.ung Liang Wang, Shu Jen Chen, Petrus Tang, Jim Tong Horng, Hsing I. Huang, Jen-Ren Wang, David M. Ojcius, Gary Brewer, Shin Ru Shih

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10(5) copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5' untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES.

Original languageEnglish
Pages (from-to)12789-12805
Number of pages17
JournalNucleic acids research
Volume42
Issue number20
DOIs
Publication statusPublished - 2014 Nov 10

Fingerprint

RNA Viruses
Viral RNA
RNA
Viruses
Small Cytoplasmic RNA
Enterovirus
5' Untranslated Regions
Viral Proteins
Virus Diseases
Northern Blotting
Insects
Cell Count

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Weng, K. F., Hung, C. T., Hsieh, P. T., Li, M. L., Chen, G. W., Kung, Y. A., ... Shih, S. R. (2014). A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic acids research, 42(20), 12789-12805. https://doi.org/10.1093/nar/gku952
Weng, Kuo Feng ; Hung, Chuan Tien ; Hsieh, Po Ting ; Li, Mei Ling ; Chen, Guang Wu ; Kung, Yu An ; Huang, Peng Nien ; Kuo, Rei Lin ; Chen, Li Lien ; Lin, Jing Yi ; Wang, Robert Y.ung Liang ; Chen, Shu Jen ; Tang, Petrus ; Horng, Jim Tong ; Huang, Hsing I. ; Wang, Jen-Ren ; Ojcius, David M. ; Brewer, Gary ; Shih, Shin Ru. / A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. In: Nucleic acids research. 2014 ; Vol. 42, No. 20. pp. 12789-12805.
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abstract = "The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10(5) copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5' untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES.",
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Weng, KF, Hung, CT, Hsieh, PT, Li, ML, Chen, GW, Kung, YA, Huang, PN, Kuo, RL, Chen, LL, Lin, JY, Wang, RYUL, Chen, SJ, Tang, P, Horng, JT, Huang, HI, Wang, J-R, Ojcius, DM, Brewer, G & Shih, SR 2014, 'A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells', Nucleic acids research, vol. 42, no. 20, pp. 12789-12805. https://doi.org/10.1093/nar/gku952

A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. / Weng, Kuo Feng; Hung, Chuan Tien; Hsieh, Po Ting; Li, Mei Ling; Chen, Guang Wu; Kung, Yu An; Huang, Peng Nien; Kuo, Rei Lin; Chen, Li Lien; Lin, Jing Yi; Wang, Robert Y.ung Liang; Chen, Shu Jen; Tang, Petrus; Horng, Jim Tong; Huang, Hsing I.; Wang, Jen-Ren; Ojcius, David M.; Brewer, Gary; Shih, Shin Ru.

In: Nucleic acids research, Vol. 42, No. 20, 10.11.2014, p. 12789-12805.

Research output: Contribution to journalArticle

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T1 - A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

AU - Weng, Kuo Feng

AU - Hung, Chuan Tien

AU - Hsieh, Po Ting

AU - Li, Mei Ling

AU - Chen, Guang Wu

AU - Kung, Yu An

AU - Huang, Peng Nien

AU - Kuo, Rei Lin

AU - Chen, Li Lien

AU - Lin, Jing Yi

AU - Wang, Robert Y.ung Liang

AU - Chen, Shu Jen

AU - Tang, Petrus

AU - Horng, Jim Tong

AU - Huang, Hsing I.

AU - Wang, Jen-Ren

AU - Ojcius, David M.

AU - Brewer, Gary

AU - Shih, Shin Ru

PY - 2014/11/10

Y1 - 2014/11/10

N2 - The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10(5) copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5' untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES.

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