4.6 Article

Processing of α-globin and ICP0 mRNA in cells infected with herpes simplex virus type 1 ICP27 mutants

Journal

JOURNAL OF VIROLOGY
Volume 74, Issue 16, Pages 7307-7319

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.74.16.7307-7319.2000

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Funding

  1. NIAID NIH HHS [R21 AI042737, R01 AI042737, AI42737] Funding Source: Medline

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Herpes simplex virus (HSV) ICP27 is an essential and multifunctional regulator of viral gene expression that modulates RNA splicing, polyadenylation, and nuclear export. We have previously reported that ICP27 causes the cytoplasmic accumulation of unspliced alpha-globin pre-mRNA. Here we examined the effects of a series of ICP27 mutations that alter important functional regions of the protein on the processing and nuclear transport of alpha-globin and HSV ICPO RNA. The results demonstrate that ICP27 mutants that are impaired for growth in noncomplementing cells, including mutants in the N- and C-terminal regions, are defective in the accumulation of alpha-globin pre-mRNA, Unexpectedly, several mutants that are competent to repress the expression of reporter genes in transient transfection assays failed to accumulate unspliced RNA, implying that different mechanisms are responsible for transrepression and pre-mRNA accumulation, Several mutants caused a marked increase in the length and heterogeneity of the alpha-globin mRNA poly(A) tail, suggesting that ICP27 may directly or indirectly affect the regulation of poly(A) polymerase, ICP27 was also required for the accumulation of multiple ICPO intron-bearing transcripts, but this effect displayed a mutational sensitivity profile different from that of accumulation of unspliced alpha-globin RNA. Moreover, unlike spliced and unspliced alpha-globin RNAs, which were efficiently exported to the cytoplasm, spliced and intron-containing ICPO transcripts were predominantly nuclear in localization, and ICP27 was not required for nuclear retention of the spliced message. We propose that these transcript- and ICP27 allele-specific differences may be explained by the presence of a strong cis-acting ICP27 response element in the alpha-globin transcript.

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