A possible role of IL-1ra 3'-untranslated region in modulation of protein production.
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.
Yamshchikov
Vladimir F
VF
Division of Gastroenterology and Hepatology, Digestive Health Center of Excellence, University of Virginia Health System, PO Box 800708, Charlottesville, VA 22908-0708, USA. vfy9e@virginia.edu
Mishina
Margarita
M
Cominelli
Fabio
F
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D015870:Gene Expression; D017930:Genes, Reporter; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008156:Luciferases / Q000235:genetics; D051379:Mice; D016296:Mutagenesis; D026723:Polyadenylation; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics*; D020298:U937 Cells
D020413:3' Untranslated Regions; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D013006:Growth Hormone; D008156:Luciferases