The 3'-untranslated region of human interleukin-8 mRNA suppresses IL-8 gene expression.
Although adenosine/uridine (AU)-rich sequences in the 3'-untranslated region (UTR) of the interleukin-8 (IL-8) gene have been suggested to contribute to its post-transcriptional regulation, the molecular basis whereby this occurs still needs to be understood. To investigate the role of the 3'-UTR on human IL-8 gene regulation, chimeric reporter genes were generated by adding full length or differentially deleted 3'-UTR of the IL-8 gene to chloramphenicol acetyltransferase (CAT). Addition of the entire IL-8 3'-UTR markedly reduced CAT mRNA and protein expression in COS 7 cells. In a reporter gene study, IL-8 3'-UTR destabilized CAT mRNA, which was dependent on active transcription in COS 7 cells. A 357-base sequence (nucleotides (nt) 2387-2743 of genomic DNA) within 3'-UTR, designated e, suppressed CAT gene expression by accelerating CAT mRNA turnover. A 26-base AU-rich sequence (nt 2552-2577) within e, containing four AUUUA pentamers that form two UAUUUAUU and one UUAUUUAU octamers, did not suppress CAT gene expression. However, deletion of the AU-rich sequences attenuated the inhibitory effect of e on CAT gene expression. Elimination of the first 100 bases (nt 2386-2486) attenuated the potency of fragment e, but much weaker than elimination of the first 146 bases (nt 2387-2533). This study gives new insights in unravelling the molecular mechanisms involved in the post-transcriptional regulation of the IL-8 gene.
Yu
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Y
Institute of Parasitology of McGill University, Ste. Anne de Bellevue, Quebec, Canada.
Chadee
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K
D020413:3' Untranslated Regions / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D015536:Down-Regulation / Q000276:immunology*; D017930:Genes, Reporter / Q000276:immunology; D000882:Haplorhini; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D016209:Interleukin-8; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase