A possible role of IL-1ra 3'-untranslated region in modulation of protein production

Abstract

Human interleukin 1 (IL-1) receptor antagonist (hIL-1ra), an anti-inflammatory cytokine and naturally occurring antagonist of IL-1, may be regulated at both the transcriptional and post-transcriptional levels. The aim of this study was to evaluate post-transcriptional regulation of hIL-1ra with specific focus on the 3'-untranslated region (3'-UTR) of hIL-1ra mRNA using the luciferase reporter gene system. Constructs were created containing the luciferase reporter gene followed by the hIL-1ra 3'-UTR or its modified variants. In monocyte/macrophage cell lines RAW264.7 and U937, the presence of the hIL-1ra 3'-UTR resulted in a 5.7-fold (n=6, P<0.001) and a 3.9-fold (n=7, P<0.001) decrease in transient reporter gene expression, respectively, with only a less than 2-fold mean difference in steady-state mRNA levels in the former case. In a cell-free translation system, the presence of the middle segment of the 3'-UTR caused a 5.2-fold (n=5, P<0.001) decrease in the amount of luciferase synthesized. In contrast to synthetic 3'-UTR and that derived from bovine growth hormone RNA, the presence of hIL-1ra 3'-UTR resulted in accumulation of unprocessed transcripts in transfected cells. We conclude that hIL-1ra synthesis may be regulated at the post-transcriptional level through mechanisms involving the 3'-UTR of IL-1ra transcripts.