Patterns of coordinate down-regulation of ARE-containing transcripts following immune cell activation.
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.
Raghavan
Arvind
A
Department of Microbiology, University of Minnesota, 420 Delaware Street, SE, MMC 196, Minneapolis, MN 55455, USA.
Dhalla
Mohammed
M
Bakheet
Tala
T
Ogilvie
Rachel L
RL
Vlasova
Irina A
IA
Khabar
Khalid S A
KS
Williams
Bryan R G
BR
Bohjanen
Paul R
PR
D015152:Blotting, Northern; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D018106:CD28 Antigens; D017252:CD3 Complex; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin