The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs.

The U(L)41 protein of herpes simplex virus 1 has been reported to mediate the degradation of both viral and cellular mRNAs. Extensive studies on beta-actin and some viral mRNAs were consonant with this conclusion. In earlier studies, we reported that the U(L)41-dependent degradation of cellular mRNAs up-regulated after infection was selective. One class of the up-regulated mRNAs, exemplified by the stress-inducible immediate-early 1 mRNA, is deadenylated, 3' to 5' degraded and is not translated. Another class of up-regulated mRNAs, exemplified by GADD45beta, does not undergo this pattern of degradation and is translated. A puzzling feature of the earlier results is that the amounts of up-regulated mRNAs accumulating in the cytoplasm of DeltaU(L)41 mutant virus-infected cells was lower than in WT virus-infected cells, a contradiction, inasmuch as if the rates of accumulation were identical and degradation of the mRNAs were higher in WT virus-infected cells, the steady-state levels should have been higher in DeltaU(L)41 mutant virus-infected cells. In this report, we show that in DeltaU(L)41 mutant virus-infected cells, the rates of degradation of the stress-inducible immediate-early response gene 1 and other up-regulated mRNAs are approximately the same as those observed in mock-infected cells and are faster than in WT virus-infected cells. This is contrary to the observed U(L)41-dependent degradation of beta-actin and other mRNAs. The U(L)41 protein thus mediates two functions, i.e., it mediates rapid degradation of some mRNAs exemplified by beta-actin and stabilizes or delays the degradation of other mRNAs exemplified by GADD45beta, tristetraprolin, etc. A model unifying both activities of the U(L)41 protein is presented.