The gene expression of two endoplasmic reticulum aminopeptidase 1 isoforms is regulated by distinct posttranscriptional mechanisms
Journal Article
·
· Biochemical and Biophysical Research Communications
- Faculty of Pharmaceutical Sciences, Teikyo-Heisei University, Nakano, Tokyo (Japan)
- Molecular Entomology Laboratory, RIKEN, Wako, Saitama (Japan)
Highlights: • ERAP1 contains two isoforms that exchange 3′ untranslated regions of mRNA. • One of ERAP1 isoform is suppressed the protein expression posttranscriptionally. • We identified cis-elements that repressed the alternative splicing within ERAP1. • IFN-γ stimulation affects transcription and the alternative splicing of ERAP1. Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a multifunctional enzyme belonging to the M1 family of aminopeptidases and shown to be associated with various autoimmune diseases. Human ERAP1 protein has two isoforms produced by alternative splicing of the 3′ terminal exon, although their functional differences have not yet been fully clarified. In this study, we showed that the isoforms undergo different posttranscriptional regulation mechanisms via their respective 3′ untranslated regions. Using a reporter system, we identified several cis-elements that are important for the regulation of alternative splicing. Finally, we revealed a close relationship between the transcriptional induction of the ERAP1 gene by interferon-gamma and the alternative splicing. These results suggest that the two ERAP1 isoforms function under different pathophysiological conditions.
- OSTI ID:
- 23134254
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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