Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b

Tomohito Matsuo, Yukiko Noguchi, Mieko Shindo, Yoshifumi Morita, Yoshie Oda, Eiko Yoshida, Hiroko Hamada, Mine Harada, Yuichi Shiokawa, Takahiro Nishida, Ryuji Tominaga, Yoshikane Kikushige, Koichi Akashi, Jun Kudoh, Nobuyoshi Shimizu, Yuka Tanaka, Tsukuru Umemura, Taketoshi Taniguchi, Akihiko Yoshimura, Takashi KobayashiMasao Mitsuyama, Hironori Kurisaki, Hitoshi Katsuta, Seiho Nagafuchi

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalGene
Volume530
Issue number1
DOIs
Publication statusPublished - Nov 1 2013

Fingerprint

Regulator Genes
3' Untranslated Regions
Autoimmune Polyendocrinopathies
Proteins
Mutation
Interleukin-2
T-Lymphocytes
HEK293 Cells
Microarray Analysis
Human Herpesvirus 4
Open Reading Frames
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Matsuo, T., Noguchi, Y., Shindo, M., Morita, Y., Oda, Y., Yoshida, E., ... Nagafuchi, S. (2013). Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b. Gene, 530(1), 19-25. https://doi.org/10.1016/j.gene.2013.08.015

Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b. / Matsuo, Tomohito; Noguchi, Yukiko; Shindo, Mieko; Morita, Yoshifumi; Oda, Yoshie; Yoshida, Eiko; Hamada, Hiroko; Harada, Mine; Shiokawa, Yuichi; Nishida, Takahiro; Tominaga, Ryuji; Kikushige, Yoshikane; Akashi, Koichi; Kudoh, Jun; Shimizu, Nobuyoshi; Tanaka, Yuka; Umemura, Tsukuru; Taniguchi, Taketoshi; Yoshimura, Akihiko; Kobayashi, Takashi; Mitsuyama, Masao; Kurisaki, Hironori; Katsuta, Hitoshi; Nagafuchi, Seiho.

In: Gene, Vol. 530, No. 1, 01.11.2013, p. 19-25.

Research output: Contribution to journalArticle

Matsuo, T, Noguchi, Y, Shindo, M, Morita, Y, Oda, Y, Yoshida, E, Hamada, H, Harada, M, Shiokawa, Y, Nishida, T, Tominaga, R, Kikushige, Y, Akashi, K, Kudoh, J, Shimizu, N, Tanaka, Y, Umemura, T, Taniguchi, T, Yoshimura, A, Kobayashi, T, Mitsuyama, M, Kurisaki, H, Katsuta, H & Nagafuchi, S 2013, 'Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b', Gene, vol. 530, no. 1, pp. 19-25. https://doi.org/10.1016/j.gene.2013.08.015
Matsuo T, Noguchi Y, Shindo M, Morita Y, Oda Y, Yoshida E et al. Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b. Gene. 2013 Nov 1;530(1):19-25. https://doi.org/10.1016/j.gene.2013.08.015
Matsuo, Tomohito ; Noguchi, Yukiko ; Shindo, Mieko ; Morita, Yoshifumi ; Oda, Yoshie ; Yoshida, Eiko ; Hamada, Hiroko ; Harada, Mine ; Shiokawa, Yuichi ; Nishida, Takahiro ; Tominaga, Ryuji ; Kikushige, Yoshikane ; Akashi, Koichi ; Kudoh, Jun ; Shimizu, Nobuyoshi ; Tanaka, Yuka ; Umemura, Tsukuru ; Taniguchi, Taketoshi ; Yoshimura, Akihiko ; Kobayashi, Takashi ; Mitsuyama, Masao ; Kurisaki, Hironori ; Katsuta, Hitoshi ; Nagafuchi, Seiho. / Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b. In: Gene. 2013 ; Vol. 530, No. 1. pp. 19-25.
@article{a8689da3a47a4699a96b393c6eb91de8,
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.",
author = "Tomohito Matsuo and Yukiko Noguchi and Mieko Shindo and Yoshifumi Morita and Yoshie Oda and Eiko Yoshida and Hiroko Hamada and Mine Harada and Yuichi Shiokawa and Takahiro Nishida and Ryuji Tominaga and Yoshikane Kikushige and Koichi Akashi and Jun Kudoh and Nobuyoshi Shimizu and Yuka Tanaka and Tsukuru Umemura and Taketoshi Taniguchi and Akihiko Yoshimura and Takashi Kobayashi and Masao Mitsuyama and Hironori Kurisaki and Hitoshi Katsuta and Seiho Nagafuchi",
year = "2013",
month = "11",
day = "1",
doi = "10.1016/j.gene.2013.08.015",
language = "English",
volume = "530",
pages = "19--25",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b

AU - Matsuo, Tomohito

AU - Noguchi, Yukiko

AU - Shindo, Mieko

AU - Morita, Yoshifumi

AU - Oda, Yoshie

AU - Yoshida, Eiko

AU - Hamada, Hiroko

AU - Harada, Mine

AU - Shiokawa, Yuichi

AU - Nishida, Takahiro

AU - Tominaga, Ryuji

AU - Kikushige, Yoshikane

AU - Akashi, Koichi

AU - Kudoh, Jun

AU - Shimizu, Nobuyoshi

AU - Tanaka, Yuka

AU - Umemura, Tsukuru

AU - Taniguchi, Taketoshi

AU - Yoshimura, Akihiko

AU - Kobayashi, Takashi

AU - Mitsuyama, Masao

AU - Kurisaki, Hironori

AU - Katsuta, Hitoshi

AU - Nagafuchi, Seiho

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84884206775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884206775&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2013.08.015

DO - 10.1016/j.gene.2013.08.015

M3 - Article

C2 - 23954874

AN - SCOPUS:84884206775

VL - 530

SP - 19

EP - 25

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1

ER -