title: Modulation by miR-29b of intestinal epithelium homoeostasis through the repression of menin translation.
abstract: Menin regulates distinct cellular functions by regulating gene transcription through its interaction with partner transcription factors, but the exact mechanisms that control menin levels remain largely unknown. In the present study we report that Men1 mRNA, encoding menin, is a novel target of miR-29b and that miR-29b/Men1 mRNA association regulates menin expression post-transcriptionally in rat intestinal epithelial cells (IECs). Overexpression of a miR-29b precursor lowered the levels of Men1 mRNA modestly, but reduced new synthesis of menin robustly; conversely, antagonism of miR-29b enhanced menin protein synthesis and steady-state levels. The repressive effect of miR-29b on menin expression was mediated through a single binding site in the coding region of Men1 mRNA, because point mutation of this site prevented miR-29b-induced repression of menin translation. Increasing cellular polyamines due to overexpression of ornithine decarboxylase (ODC) enhanced menin translation by reducing miR-29b, whereas polyamine depletion by inhibiting ODC increased it, thus suppressing menin expression. Moreover, an increase in menin abundance in an miR-29b-silenced population of IECs led to increased sensitivity to apoptosis, which was prevented by silencing menin. These findings indicate that miR-29b represses translation of Men1 mRNA, in turn affecting intestinal epithelial homoeostasis by altering IEC apoptosis.
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Miao
authors.initials: M
authors.lastname: Ouyang
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Weijie
authors.initials: W
authors.lastname: Su
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Li
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Turner
authors.affiliation: ‡Laboratory of Genetics, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD, U.S.A.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: *Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015317:Biogenic Polyamines / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D007413:Intestinal Mucosa / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015317:Biogenic Polyamines; C526366:MIRN29 microRNA, rat; C532041:Men1 protein, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D009955:Ornithine Decarboxylase