T cell activation induces a noncoding RNA transcript sensitive to inhibition by immunosuppressant drugs and encoded by the proto-oncogene, BIC.
In a search for novel early T cell activation transcripts, we identified expressed sequence tags (ESTs) more abundantly expressed in normal human CD4(+) T lymphocytes fully activated by a 5 h exposure to CD3 plus CD28 mAbs, compared to the same cells stimulated with either CD3 mAb or CD28 mAb alone. An EST was identified that hybridized with a 1.7 kb transcript expressed in activated T cells but was undetectable by Northern blot analysis in resting T cells or other normal tissues. The T cell transcript was maximally induced within 6 h and remained elevated for at least 47 h. Induction of the transcript was blocked by cyclosporin A, FK506, and dexamethasone but not by rapamycin. The transcript was polyadenylated but lacked an open reading. A BLAST search of the NCBI database revealed that the transcript shared identity with the recently reported human BIC proto-oncogene that encodes a noncoding mRNA (W. Tam, Gene 274 (2001) 157). Our data demonstrate that transcriptional activation of the BIC proto-oncogene is an early and sustained T cell activation event and suggest an important role for noncoding mRNA in T cell function.
Haasch
Deanna
D
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.
Chen
Yung-Wu
YW
Reilly
Regina M
RM
Chiou
X Grace
XG
Koterski
Sandra
S
Smith
Morey L
ML
Kroeger
Paul
P
McWeeny
Kerri
K
Halbert
Donald N
DN
Mollison
Karl W
KW
Djuric
Stevan W
SW
Trevillyan
James M
JM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics; D016559:Tacrolimus / Q000494:pharmacology; D014018:Tissue Distribution; D014158:Transcription, Genetic; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D007166:Immunosuppressive Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D022661:RNA, Untranslated; D003907:Dexamethasone; D016572:Cyclosporine; D016559:Tacrolimus