Induction of T-cell receptor-alpha and -beta mRNA in SL12 cells can occur by transcriptional and post-transcriptional mechanisms.
Genes encoding the alpha and beta subunits of the T-cell receptor (TCR) for antigen require rearrangement events for functional expression. In the case of the immunoglobin genes, rearrangement events have been shown to be necessary, but they are not sufficient for full gene expression. The regulation of TCR genes, apart from the requirement for rearrangement, remains to be elucidated. The T-lymphoma cell clone SL12.4 actively transcribes both TCR-alpha and -beta genes and the cells contain nuclear TCR precursor transcripts. However, the cells fail to accumulate appreciable quantities of mature TCR-alpha and -beta mRNAs in either the nucleus or the cytoplasm. The protein synthesis inhibitor cycloheximide (CHX) induces a 20-fold increase in mature TCR-alpha transcript accumulation without a concomitant increase in TCR-alpha gene transcription suggesting that CHX reverses the nuclear post-transcriptional events which prevent mature TCR-alpha mRNA accumulation. CHX also induces full length TCR-beta transcripts greater than 90-fold while TCR-beta gene transcription increases only 2- to 4-fold. The calcium ionophore A23187 induces the accumulation of TCR-alpha but not -beta transcripts; and in contrast to CHX, it increases the rate of TCR-alpha gene transcription and the expression of large nuclear TCR-alpha precursor transcripts. Since CHX and A23187 mediated induction of TCR mRNA is both rapid and reversible, it is unlikely that new DNA rearrangements are responsible for the induction. Collectively, the data show that the accumulation of mature TCR-alpha and -beta transcripts in SL12.4 cells can be coordinately or independently induced by nuclear events involving both transcriptional and posttranscriptional mechanisms.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D005796:Genes; D046911:Macromolecular Substances; D009693:Nucleic Acid Hybridization; D010142:Pactamycin / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D046911:Macromolecular Substances; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D010142:Pactamycin; D000001:Calcimycin; D003513:Cycloheximide