Regulation of rantes gene expression by a 3′-utr that lacks consensus sites for mrna turnover

E. Sardifia, R. Tidwell, T. Koga, M. J. Holtzman

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1 Scopus citations

Abstract

Analysis of the host response to viral infection has focused on the capacity of viruses to activate or repress transcription of cellular genes, and this approach is also characteristic of work on paramyxoviruses such as respiratory syncytial virus (RSV). Our work indicates that RSV replication or interferon (IFN)-Y treatment upregulates expression of a subset of immune-response genes in the airway epithelium by mRNA stabilization as well as increased gene transcription. In fact, experiments with isolated airway epithelial cells indicate that virus- and IFN-y-inducible expression of one critical immune-response gene-the -chemokine RANTES-exhibits a distinct requirement for mRNA stabilization. In addition, it appeared that the regulatory sites for controlling basal and inducible RANTES gene expression were contained in the mature mRNA but not in the poly(A) tail. To now define the cis-actine mRNA turnover elements that regulate basal instability of RANTES mRNA, we monitored the expression level of reporter plasmids containing portions or all of the three exons encoding the RANTES gene placed in the context of a luciferase reporter fragment and a heterologous gene promoter. RNase protection assays for luciferase mRNA levels indicated that expression was markedly increased by deletion of the RANTES 3'-UTR even though this region contains no AU- or GC-rich elements that have been implicated in mediating cytokine- or virus-inducible alterations in mRNA stability in other genes. Taken together, the results suggest that distinct sites in the RANTES 3′-UTR confer basal susceptibility to endoribonucleases and that these sites may be targets for reversal when the infected cell takes advantage of viral machinery or responds to IFN-γ to mediate host defense.

Original languageEnglish
Pages (from-to)A1308
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

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