Induction of 150-kDa adenosine deaminase that acts on RNA (ADAR)-1 gene expression in normal T lymphocytes by anti-CD3-epsilon and anti-CD28.
We and other investigators have demonstrated up-regulation of the expression of the RNA-editing gene 150-kDa adenosine deaminase that acts on RNA (ADAR1) in systemic lupus erythematosus (SLE) T cells and B cells, peripheral blood mononuclear cells (PBMC), natural killer (NK) cells. The presence of a small proportion of activated T cells is the hallmark of SLE. Therefore, it was hypothesized that 150-kDa ADAR1 gene expression is induced by the physiological activation of T cells. To examine this hypothesis, normal T cells were activated by anti-CD3-epsilon plus anti-CD28 for various time periods from 0 to 48 hr. The expression of 110-kDa and 150-kDa ADAR1, and interleukin (IL)-2 and beta-actin gene transcripts was analysed. An approximately fourfold increase in 150-kDa ADAR1 gene expression was observed in activated T cells. ADAR2 gene transcripts are substrates for ADAR1 and ADAR2 enzymes. Therefore, we assessed the role of the 150-kDa ADAR enzyme in editing of ADAR2 gene transcripts. In activated T cells, site-selective editing of the -2 site was observed. Previous studies indicate that this site is predominantly edited by ADAR1. In addition to this, novel editing sites at base positions -56, -48, -45, -28, -19, -15, +46 and +69 were identified in activated T cells. On the basis of these results, it is proposed that 150-kDa ADAR1 gene expression is selectively induced in T cells by anti-CD3-epsilon and anti-CD28 stimulation and that it may play a role in site-selective editing of gene transcripts and in altering the functions of several gene products of T cells during activation and proliferation.
Laxminarayana
Dama
D
Section on Rheumatology and Immunology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. dLaxmina@wfubmc.edu
Khan
Islam U
IU
O'Rourke
Kenneth S
KS
Giri
Banabihari
B
D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009154:Mutation; D017393:RNA Editing; D012318:RNA Polymerase I; D016601:RNA-Binding Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000276:immunology
D018106:CD28 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; C119975:POLR1G protein, human; D012318:RNA Polymerase I; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase