mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice

• mmu-miR-702 is down-regulated in ISO-induced apoptosis while ATF6 is up-regulated.
• Over-expression of mmu-miR-702 can inhibit the expression of ATF6 protein.
• Over-expression of mmu-miR-702 can abrogate the ISO-induced apoptosis.

MicroRNAs (miRNAs) are a group of endogenous, small, noncoding RNAs that function as key post-transcriptional regulators. miRNAs are involved in many biological processes including apoptosis. In this study, mouse miR-702 (mmu-miR-702), a mirtron derived from the 13th intron of the Plod3 gene, was identified as a regulator of anti-apoptosis. mmu-miR-702 was down-regulated after treatment with the apoptosis-inducer isoproterenol both in vivo and in vitro. According to over-expression experiments, mmu-miR-702 inhibited apoptosis as well as the expression levels of a subset of apoptosis-related genes including activating transcription factor 6 (ATF6). An interaction between mmu-miR-702 and the ATF6 3′-UTR binding site was confirmed using luciferase reporter and western blot assays. This is the first report of ATF6 interaction with miRNA. Although the possible existence of miR-702 in the human genome is low, our results indicate that mirtrons also participate in the process of apoptosis and may provide a novel study strategy for apoptosis.