title: The UL41 protein of herpes simplex virus mediates selective stabilization or degradation of cellular mRNAs.
abstract: 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.
authors.affiliation: The Marjorie Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Esclatine
authors.forename: Brunella
authors.initials: B
authors.lastname: Taddeo
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
mesh_terms: D020413:3' Untranslated Regions; D000943:Antigens, Differentiation / Q000378:metabolism; D015152:Blotting, Northern; D003593:Cytoplasm / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000378:metabolism; D006801:Humans; D009154:Mutation; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000378:metabolism*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D020413:3' Untranslated Regions; D000943:Antigens, Differentiation; D012313:RNA; D012333:RNA, Messenger; D014404:Tubulin; D014764:Viral Proteins; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C081688:Ul41 protein, Human herpesvirus 1