The 3' untranslated region of IL-1beta regulates protein production.
IL-1beta, a pro-inflammatory cytokine, has sequences in its 3' untranslated region (UTR) that may play a role in the post-transcriptional regulation of IL-1beta production. To test this hypothesis, a series of chimeric reporter genes were developed consisting of a chloramphenicol acetyltransferase (CAT) gene the native 3'-UTR of which was replaced by the full-length IL-1beta 3'-UTR or various 3'-UTR deletion mutants. Expression of these constructs under the SV40 late promoter in THP-1 cells showed that the full-length 3'-UTR repressed constitutive CAT activity to 28% of control CAT activity. Further analysis of the 3'-UTR localized the repressor signal to an adenosine-thymidine (AdT)-rich region. Upon exposure to LPS, the full-length IL-1beta 3'-UTR mediated almost a fivefold increase in CAT activity. The LPS response was not simply loss of AdT-mediated repression; when this sequence was tested alone, it did not respond to LPS. The LPS response effect was localized to the terminal 177 base pairs of the IL-1beta 3'-UTR. The increase in CAT activity following LPS stimulation was associated with an increased CAT.IL-1beta 3'-UTR mRNA half-life, indicating at least one effect of the 3'-UTR on a post-transcriptional process. These studies demonstrate that the IL-1beta 3'-UTR is involved in the regulation of IL-1beta protein production, and a LPS response element may be in the IL-1beta 3'-UTR.
Kern
J A
JA
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Warnock
L J
LJ
McCafferty
J D
JD
D002460:Cell Line; D002678:Chimera; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic
D007375:Interleukin-1; D012333:RNA, Messenger