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Chunk #19 — RESULTS — IRE1α utilizes a micro-RNA to control TXNIP levels

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IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress.
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mRNA stability is often governed by binding of specific microRNAs to complementary sequences in the 3′-untranslated region (UTR) of gene targets (Fabian et al., 2010). Bioinformatic analysis of the TXNIP 3′-UTR identified two conserved binding sites for microRNA-17 (miR-17) (Figure 3C). This provoked the hypothesis that changes in miR-17 may regulate TXNIP mRNA stability. Consistent with this notion, we find that miR-17 levels rapidly decline under ER stress, but not under high glucose (Figure 3D). TXNIP mRNA levels can be increased by introducing anti-miR-17 into cells (Figure 3E); conversely a miR-17 mimic reduces baseline levels of TXNIP mRNA (Figure 3F).