Opposite to its effects on miR-17, forcible activation of IRE1α is sufficient to induce TXNIP mRNA, even without ER stress, and endogenous IRE1α is necessary for TXNIP induction under irremediable ER stress. Thus, a parsimonious interpretation holds that IRE1α controls TXNIP mRNA levels—in part—post-transcriptionally by regulating levels of its repressive miR-17. We are investigating whether decreases in miR-17 proceed directly from endonucleolytic cleavage by IRE1α RNase, as we found for decay of ER-localized mRNAs (Han et al., 2009).
