Raghavan Arvind, Dhalla Mohammed, Bakheet Tala, Ogilvie Rachel L, Vlasova Irina A, Khabar Khalid S A, Williams Bryan R G, Bohjanen Paul R
Department of Microbiology, University of Minnesota, 420 Delaware Street, SE, MMC 196, Minneapolis, MN 55455, USA.
Genomics. 2004 Dec;84(6):1002-13. doi: 10.1016/j.ygeno.2004.08.007.
We evaluated the expression of over 900 AU-rich element (ARE)-containing transcripts in primary human T lymphocytes following stimulation with anti-CD3 and anti-CD28 antibodies and found that approximately 48% of these transcripts were regulated following T cell activation. We identified approximately 145 ARE-containing transcripts that were rapidly induced and then rapidly disappeared within 1 h after activation. Another 250 ARE-containing transcripts expressed in resting T cells were rapidly turned off within 30 min after activation. The rates of transcript disappearance correlated well with rapid mRNA decay measured following transcriptional arrest with actinomycin D. We identified a subset of ARE-containing transcripts that were rapidly induced following T cell activation that were also induced following lipopolysaccharide stimulation of THP-1 monocytes, and these transcripts exhibited rapid decay in both cell types. Our results suggest that ARE-mediated mRNA decay plays an important role in the precisely coordinated down-regulation of gene expression following immune cell activation.
我们评估了原代人T淋巴细胞在用抗CD3和抗CD28抗体刺激后900多个含富含AU元件（ARE）转录本的表达情况，发现这些转录本中约48%在T细胞活化后受到调控。我们鉴定出约145个含ARE的转录本在活化后迅速被诱导，然后在1小时内迅速消失。另外250个在静息T细胞中表达的含ARE转录本在活化后30分钟内迅速关闭。转录本消失的速率与用放线菌素D阻断转录后测得的mRNA快速降解密切相关。我们鉴定出一组含ARE的转录本，它们在T细胞活化后迅速被诱导，在脂多糖刺激THP-1单核细胞后也被诱导，并且这些转录本在两种细胞类型中均表现出快速降解。我们的结果表明，ARE介导的mRNA降解在免疫细胞活化后基因表达的精确协同下调中起重要作用。
