Cytoplasmic Viral RNA-Dependent RNA Polymerase Disrupts the Intracellular Splicing Machinery by Entering the Nucleus and Interfering with Prp8

Yen Chin Liu, Rei Lin Kuo, Jing Yi Lin, Peng Nien Huang, Yi Huang, Hsuan Liu, Jamine J. Arnold, Shu Jen Chen, Robert Yung Liang Wang, Craig E. Cameron, Shin Ru Shih

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp) is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3Dpol) also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3Dpol enters the nucleus through the nuclear localization signal (NLS) and targets the pre-mRNA processing factor 8 (Prp8) to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3Dpol associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3Dpol complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.

Original languageEnglish
Article numbere1004199
JournalPLoS Pathogens
Volume10
Issue number6
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology
  • Medicine(all)

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    Liu, Y. C., Kuo, R. L., Lin, J. Y., Huang, P. N., Huang, Y., Liu, H., Arnold, J. J., Chen, S. J., Wang, R. Y. L., Cameron, C. E., & Shih, S. R. (2014). Cytoplasmic Viral RNA-Dependent RNA Polymerase Disrupts the Intracellular Splicing Machinery by Entering the Nucleus and Interfering with Prp8. PLoS Pathogens, 10(6), [e1004199]. https://doi.org/10.1371/journal.ppat.1004199