Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.

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 (3D(pol)) also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol) 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 3D(pol) 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 Prp8-3D(pol) 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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Liu YC,Kuo RL,Lin JY,Huang PN,Huang Y,Liu H,Arnold JJ,Chen SJ,Wang RY,Cameron CE,Shih SR

doi

10.1371/journal.ppat.1004199

subject

Has Abstract

pub_date

2014-06-26 00:00:00

pages

e1004199

issue

6

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-13-03244

journal_volume

10

pub_type

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