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J Immunol. 2013 Aug 15;191(4):1907-15. doi: 10.4049/jimmunol.1201925. Epub 2013 Jul 12.

Novel role for molecular transporter importin 9 in posttranscriptional regulation of IFN-ε expression.

Author information

1
Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. tomo1027@cc.hirosaki-u.ac.jp

Abstract

IFN-ε is a unique type I IFN whose constitutive expression in lung, brain, small intestine, and reproductive tissues is only partially understood. Our previous observation that posttranscriptional events participate in the regulation of IFN-ε mRNA expression led us to investigate whether the 5' and/or 3' untranslated regions (UTR) have regulatory functions. Surprisingly, we found that full-length IFN-ε 5'UTR markedly suppressed mRNA expression under basal conditions. Analysis of the secondary structure of this region predicted formation of two stable stem-loop structures, loops 1 and 2. Studies using luciferase constructs harboring various stretches of IFN-ε 5'UTR and mutant constructs in which the conformation of loop structures was disrupted showed that loop 1 is essential for regulation of mRNA expression. Incubation of HeLa cell extracts with agarose-bound RNAs harboring IFN-ε loop structures identified importin 9 (IPO9), a molecular transporter and chaperone, as a candidate that associates with these regions of the 5'UTR. IPO9 overexpression decreased, and IPO9 silencing increased basal IFN-ε expression. Our studies uncover a previously undescribed function for IPO9 as a specific, and negative, posttranscriptional regulator of IFN-ε expression, and they identify key roles for IFN-ε stem-loop structure 1 in this process. IPO9-mediated effects on 5'UTRs appear to extend to additional mRNAs, including hypoxia-inducible factor-1α, that can form specific loop structures.

PMID:
23851686
PMCID:
PMC3758363
DOI:
10.4049/jimmunol.1201925
[Indexed for MEDLINE]
Free PMC Article

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