Gerez L, Arad G, Efrat S, Ketzinel M, Kaempfer R
Department of Molecular Virology, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
J Biol Chem. 1995 Aug 18;270(33):19569-75. doi: 10.1074/jbc.270.33.19569.
Interleukin-2 (IL-2) regulates the clonal expansion of activated T cells and is produced in limited amounts during an immune response. Mitogenic induction of human IL-2 gene expression elicits a transient wave of unstable mRNA. We show here that transcription continues unabated during and well beyond the time when the wave is subsiding, yet few, if any, new mRNA molecules are generated once the wave has reached its maximum. Instead, IL-2 precursor transcripts accumulate, becoming the majority of expressed IL-2 RNA molecules. The flow of precursor transcripts into mature mRNA becomes inhibited in the course of induction. When translation is blocked (e.g. by cycloheximide), expression of IL-2 mRNA can be superinduced by 2 orders of magnitude. This superinduction is completely dependent upon transcription, yet is not accompanied by any significant increase in the rate of primary transcription or in mRNA stability. Instead, the processing of nuclear IL-2 precursor transcripts is greatly facilitated, resulting in pronounced superinduction of cytoplasmic mRNA. Once its transcription has been induced, therefore, expression of the IL-2 gene is down-regulated extensively at the level of precursor RNA processing.
白细胞介素-2（IL-2）调节活化T细胞的克隆扩增，并且在免疫反应期间少量产生。人IL-2基因表达的促有丝分裂诱导引发不稳定mRNA的短暂波动。我们在此表明，在波动消退期间及之后很长时间，转录仍未减弱，但一旦波动达到最大值，几乎没有新的mRNA分子产生。相反，IL-2前体转录本积累，成为表达的IL-2 RNA分子的主要部分。在诱导过程中，前体转录本向成熟mRNA的流动受到抑制。当翻译被阻断（例如用环己酰亚胺）时，IL-2 mRNA的表达可被超诱导2个数量级。这种超诱导完全依赖于转录，但初级转录速率或mRNA稳定性没有任何显著增加。相反，核IL-2前体转录本的加工得到极大促进，导致细胞质mRNA明显超诱导。因此，一旦IL-2基因的转录被诱导，其表达在前体RNA加工水平上被广泛下调。
