title: Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b.
abstract: Although mutations of autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), presenting a wide spectrum of many characteristic and non-characteristic clinical features, some patients lack AIRE gene mutations. Therefore, something other than a mutation, such as dysregulation of AIRE gene, may be a causal factor for APECED or its related diseases. However, regulatory mechanisms for AIRE gene expression and/or translation have still remained elusive. We found that IL-2-stimulated CD4(+) T (IL-2T) cells showed a high expression of AIRE gene, but very low AIRE protein production, while Epstein-Barr virus-transformed B (EBV-B) cells express both AIRE gene and AIRE protein. By using microarray analysis, we could identify miR-220b as a possible regulatory mechanism for AIRE gene translation in IL-2T cells. Here we report that miR-220b significantly reduced the expression of AIRE protein in AIRE gene with 3'UTR region transfected 293T cells, whereas no alteration of AIRE protein production was observed in the open reading frame of AIRE gene alone transfected cells. In addition, anti-miR-220b reversed the inhibitory function of miR-220b for the expression of AIRE protein in AIRE gene with 3'UTR region transfected cells. Moreover, when AIRE gene transfected cells with mutated 3'UTR were transfected with miR-220b, no reduction of AIRE protein production was observed. Taken together, it was concluded that miR-220b inhibited the AIRE gene translation through the 3'UTR region of AIRE gene, indicating that miR-220b could serve as a regulator for human AIRE gene translation.
authors: Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Tomohito
authors: T
authors: Matsuo
authors: Yukiko
authors: Y
authors: Noguchi
authors: Mieko
authors: M
authors: Shindo
authors: Yoshifumi
authors: Y
authors: Morita
authors: Yoshie
authors: Y
authors: Oda
authors: Eiko
authors: E
authors: Yoshida
authors: Hiroko
authors: H
authors: Hamada
authors: Mine
authors: M
authors: Harada
authors: Yuichi
authors: Y
authors: Shiokawa
authors: Takahiro
authors: T
authors: Nishida
authors: Ryuji
authors: R
authors: Tominaga
authors: Yoshikane
authors: Y
authors: Kikushige
authors: Koichi
authors: K
authors: Akashi
authors: Jun
authors: J
authors: Kudoh
authors: Nobuyoshi
authors: N
authors: Shimizu
authors: Yuka
authors: Y
authors: Tanaka
authors: Tsukuru
authors: T
authors: Umemura
authors: Taketoshi
authors: T
authors: Taniguchi
authors: Akihiko
authors: A
authors: Yoshimura
authors: Takashi
authors: T
authors: Kobayashi
authors: Masao
authors: M
authors: Mitsuyama
authors: Hironori
authors: H
authors: Kurisaki
authors: Hitoshi
authors: H
authors: Katsuta
authors: Seiho
authors: S
authors: Nagafuchi
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology / Q000821:virology; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D007376:Interleukin-2; D035683:MicroRNAs; D014157:Transcription Factors; D000096927:AIRE Protein; C584838:MIRN220 microRNA, human
keywords: AIRE; APECED; APS-1; Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; Autoimmune regulator gene; EBV-B; Epstein–Barr virus transformed B; IL-2T; MicroRNA; OTC-4 cells transfected with AIRE cDNA; OTC-4-AIRE; Translation; antigen and IL-2-stimulated CD4(+) T; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; autoimmune polyglandular syndrome type 1; autoimmune regulator