title: Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical Science College, Harbin Medical University, Harbin 150081, China.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Qin
authors.initials: Q
authors.lastname: Dong
authors.forename: Juan
authors.initials: J
authors.lastname: He
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Zhao
authors.forename: Feng-Lan
authors.initials: FL
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D051702:Activating Transcription Factor 6 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D057809:HEK293 Cells; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D041681:NIH 3T3 Cells
chemical_list: D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D035683:MicroRNAs; C577875:Mirn702 microRNA, mouse; D007545:Isoproterenol
keywords: 78kDa glucose-regulated protein; ATF6; Apoptosis; B-cell CLL/lymphoma 2; BAX; BCL2; BCL2-associated X protein; C/EBP homologous protein; CHOP; ER; ERSE; GRP78; ISO; Isoproterenol; MicroRNA; Short hairpin introns; UPR; UTR; X-box binding protein 1; XBP1; activating transcription factor 6; endoplasmic reticulum; endoplasmic reticulum stress response element; isoproterenol; miR-702; mmu-miR-702; mouse microRNA-702; unfolded protein response; untranslated regions