Adenovirus early region 4 promotes the localization of splicing factors and viral RNA in late-phase interchromatin granule clusters.

Adenovirus early region 4 (E4) mutants are defective for late gene expression and show reduced levels of late RNA in both the cytoplasm and the nucleus. These reductions reflect a posttranscriptional defect in the production of viral late RNA. We find that E4 mutants form replication centers during the initial stages of infection and are able to redistribute splicing factors to transcription sites that surround viral replication centers. However, E4 mutant infected cultures have reduced numbers of cells with splicing factors localized in enlarged interchromatin granule clusters during the late phase. Although the late-phase interchromatin granule clusters that formed in wild-type and E4 mutant infected cells had similar levels of poly(A) RNA, they contained reduced levels of viral RNA. These results suggest that E4 mutants do not efficiently accumulate viral late RNA in late-phase interchromatin granule clusters following the onset of late RNA transcription.