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

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RNA-dependent RNA polymerase (RdRp) is an enzyme that catalyzes the replication from an RNA template and is encoded in the genomes of all RNA viruses. RNA viruses in general replicate in cytoplasm and interfere host cellular gene expression by utilizing proteolytic destruction of cellular targets as the primary mechanism. However, several cytoplasmic RNA viral proteins have been found in the nucleus. What do they do in the nucleus? This study utilized picornaviral polymerase to probe the function of RdRp in the nucleus. Our findings reveal a novel mechanism of viruses attacking hosts whereby picornaviral 3D polymerase (3Dpol) enters the nucleus and targets the central pre-mRNA processing factor 8 (Prp8) to block pre-mRNA splicing and mRNA synthesis. The 3Dpol inhibits the second catalytic step of the splicing process, resulting in the accumulation of the lariat-form and the reduction of the mRNA. These results provide new insights into the strategy of a cytoplasmic RNA virus attacking host cell, that differs from viral shutting off cellular transcription and translation which contributes to the viral pathogenesis. To our knowledge, this study shows for the first time that a cytoplasmic RNA virus uses its polymerase to alter cellular gene expression by hijacking the splicing machinery.

Vyšlo v časopise: Cytoplasmic Viral RNA-Dependent RNA Polymerase Disrupts the Intracellular Splicing Machinery by Entering the Nucleus and Interfering with Prp8. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004199
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004199

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