A herpesvirus regulatory protein appears to act post-transcriptionally by affecting mRNA processing

Post-transcriptional control mechanisms play an important role in regulating gene expression for a number of viruses, especially in the regulation of late gene products. In this study we have investigated the mode of action of ICP27, an immediate-early regulatory protein of herpes simplex virus 1 (HSV-1) required for late gene expression. Transfection experiments have demonstrated that ICP27 can activate or repress expression depending on the target gene. Here, we show that the regulatory activity of ICP27 is independent of the target gene promoter sequences but, instead, depends on the presence of different mRNA processing signals. The activation function correlated with different polyadenylation sites, whereas the repressor function correlated with the presence of introns either 5' or 3' to the target gene-coding sequences. Poly(A)+ RNA levels were increased by ICP27 in transfections with a target gene having only an AATAAA recognition signal but no G/U box within the usual distance. In contrast, in the presence of ICP27, spliced target mRNAs were decreased 5- to 10-fold in transfections with target genes containing a 5' or 3' intron. These results suggest that this essential HSV-1 regulatory protein acts post-transcriptionally to affect mRNA processing and point to possible interactions between splicing and polyadenylation factors.