Herpes simplex virus trans-regulatory protein ICP27 stabilizes and binds to 3' ends of labile mRNA.

Abstract:

:Previous work demonstrated that a herpes simplex virus type 1 (HSV-1) immediate-early function up-regulates beta interferon but not chloramphenicol acetyltransferase reporter genes driven by the strong simian virus 40 (SV40) or cytomegalovirus promoter-enhancer regions in both transient assays and stable cell lines. The different 3' mRNA stabilization and RNA-processing signals from these two reporter genes appeared to be primarily responsible for this phenomenon. We now report that the HSV-1 ICP27 itself is sufficient to stimulate both steady-state accumulation and increased half-life of beta interferon reporter gene mRNA. Furthermore, the ability to respond directly to cotransfected ICP27 can be transferred to chloramphenicol acetyltransferase reporter genes by replacement of their SV40-derived splicing and poly(A) signals with the 3' AU-rich and poly(A) RNA-processing signals from the normally highly labile beta interferon and c-myc mRNA species. ICP27 expressed in bacteria bound specifically to in vitro-generated RNA from both the beta interferon and c-myc intronless AU-rich 3' RNA-processing regions, but not to the SV40-derived early-region splice signal and poly(A) sequences. By site-specific mutagenesis, we also show that individual ICP27 C-terminal amino acid residues that are positionally conserved in ICP27 homologs in other herpesviruses (D-357, E-358, H-479, C-400, C-483, and C-488) are critical for trans-regulatory activity. Importantly, several of these positions match mutations that are known to be essential for the role of ICP27 in the early-to-late switch during the virus lytic cycle. Therefore, our findings support the notion that HSV ICP27 modulates gene expression posttranscriptionally in part by targeting RNA.

journal_name

J Virol

journal_title

Journal of virology

authors

Brown CR,Nakamura MS,Mosca JD,Hayward GS,Straus SE,Perera LP

doi

10.1128/JVI.69.11.7187-7195.1995

subject

Has Abstract

pub_date

1995-11-01 00:00:00

pages

7187-95

issue

11

eissn

0022-538X

issn

1098-5514

journal_volume

69

pub_type

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