Post-transcriptional processing of cellular RNAs in herpes simplex virus-infected cells.
In HSV-1 (herpes simplex virus 1)-infected cells, the U(L)41 gene product carried with the virion has been shown to mediate the degradation of mRNA, leading to the shut-off of cellular protein synthesis. Analysis of the RNAs accumulating in cells infected with HSV-1 revealed the accumulation of RNAs encoding numerous cellular proteins both associated with and independent of activation of the NF-kappaB (nuclear factor kappaB) pathway. Studies on the activation of NF-kappaB and the expression and fate of selected cellular transcripts revealed the following. (i) In HSV-1-infected cells, NF-kappaB is activated by activated protein kinase R. Furthermore, the blockade of NF-kappaB translocation by suppression of protein kinase R activation does not render the cell more susceptible to apoptosis induced by viral gene expression. (ii) A number of mRNA up-regulated in infected cells [e.g. IkappaBalpha (inhibitory kappaBalpha), the immediate-early response protein IEX-1 and c-fos] are partially degraded and not translated. The degradation is U(L)41-dependent and results in deadenylation, endonucleolytic cleavage and 3'-5' degradation. The 5'-portion resulting from the endonucleolytic cleavage tends to linger in the infected cells. To date, the RNAs processed in this manner contained ARE (AU-rich elements) in their 3'-untranslated domains. RNAs lacking ARE were expressed and not degraded in this manner. (iii) Tristetraprolin and T-cell internal antigen-1, cellular proteins involved in the degradation of ARE-containing RNAs, are induced and activated in infected cells and tristetraprolin interacts physically with the U(L)41 protein.
Taddeo
B
B
The Marjorie Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA.
Esclatine
A
A
Roizman
B
B
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D039102:Poly(A)-Binding Proteins; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018139:Simplexvirus / Q000378:metabolism*; D000074019:T-Cell Intracellular Antigen-1; D051816:Tristetraprolin; D015854:Up-Regulation
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D000072000:NF-KappaB Inhibitor alpha; C076751:TIAL1 protein, human; D012313:RNA