RNA processing is a limiting step for murine tumor necrosis factor beta expression in response to interleukin-2.
We have previously reported that tumor necrosis factor beta (TNF beta) expression is induced by interleukin-2 (IL-2) in the murine lymphocytic T-cell line CTLL-2. In this study, we have characterized the nuclear and cytoplasmic TNF beta transcript and assessed their role in TNF beta gene expression. A unique feature of TNF beta expression was the accumulation of nuclear precursors, which reflected a slow nuclear RNA processing. As a consequence, there was a delay in the appearance of cytoplasmic messengers after the transcriptional induction of TNF beta by IL-2. We also found that two messengers, the fully spliced messenger and an intron 3-retaining messenger, were exported to the cytoplasm and actively translated. The same pattern of expression was observed in concanavalin A-stimulated splenocytes, although the level of expression was much lower than in CTLL-2 cells. The simple genetic structure and the high level of accumulation of nuclear precursors make TNF beta a particularly attractive model system to use for studies of RNA processing and cytoplasmic transport of partially spliced messengers.
Laboratoire d'Oncologie Moléculaire, Institut Gustave Roussy, Centre National de la Recherche Scientifique UA 1158, Villejuif, France.
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Weil
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Brosset
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Dautry
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D005091:Exons; D015723:Gene Library; D007376:Interleukin-2 / Q000494:pharmacology*; D007438:Introns; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic; D014158:Transcription, Genetic
D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D003208:Concanavalin A; D012313:RNA