The gene expression of two endoplasmic reticulum aminopeptidase 1 isoforms is regulated by distinct posttranscriptional mechanisms

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 function...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-09, Vol.503 (4), p.3180-3185
Main Authors: Aoki, Kazuma, Furuya, Akemi, Matsumoto, Ken, Tsujimoto, Masafumi
Format: Article
Language:English
Subjects:
3' Untranslated Regions
60 APPLIED LIFE SCIENCES
Alternative Splicing
AMINOPEPTIDASES
Aminopeptidases - genetics
ENDOPLASMIC RETICULUM
Endoplasmic reticulum aminopeptidase 1
EXONS
HeLa Cells
Humans
INTERFERON
Interferon-gamma
Interferon-gamma - metabolism
MESSENGER-RNA
Minor Histocompatibility Antigens - genetics
Protein Isoforms - genetics
RNA, Messenger - genetics
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Summary: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. [Display omitted] •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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.08.117