Induction of 150-kDa adenosine deaminase that acts on RNA (ADAR)-1 gene expression in normal T lymphocytes by anti-CD3-ε and anti-CD28

Dama Laxminarayana, Islam U. Khan, Kenneth S. O'Rourke, Banabihari Giri

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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-ε 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 β-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-ε 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.

Original languageEnglish (US)
Pages (from-to)623-633
Number of pages11
JournalImmunology
Volume122
Issue number4
DOIs
StatePublished - Dec 1 2007

Keywords

  • Gene transcripts
  • Mutations
  • RNA editing
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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