RRC ID 44596
Author 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.
Title Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b.
Journal Gene
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.
Volume 530(1)
Pages 19-25
Published 2013-11-1
DOI 10.1016/j.gene.2013.08.015
PII S0378-1119(13)01045-7
PMID 23954874
MeSH CD4-Positive T-Lymphocytes / metabolism Gene Expression Regulation / genetics Herpesvirus 4, Human / genetics Humans Interleukin-2 / metabolism* MicroRNAs / genetics* Mutation Polyendocrinopathies, Autoimmune / genetics* Polyendocrinopathies, Autoimmune / immunology Polyendocrinopathies, Autoimmune / virology Protein Biosynthesis Transcription Factors / genetics*
IF 2.984
Times Cited 10
Human and Animal Cells K562 ATN-1(RCB1440)