Calcium-dependent and oncogenic IL-3 mRNA stabilization can be distinguished pharmacologically and by sequence requirements in the 3'UTR.
In interleukin-3 (IL-3)-dependent PB-3c mast cells, the normally short-lived IL-3 mRNA is stabilized upon calcium-ionophore treatment or following v-H-ras induced oncogenesis. We compared the underlying stabilization mechanisms by analysing the response to the post-transcriptionally acting drugs cyclosporin A (CsA), FK506 and SB202190. Stable IL-3 transcripts in the PB-3c-derived tumour cell line V2D1 decayed in response to CsA and FK506, but not in response to SB202190. Transcripts stabilized by elevating intracellular calcium levels in PB-3c cells were destabilized in response to all three drugs. In PB-3c cells, six AUUUA pentamers within the AU-rich element were sufficient to confer responsiveness to calcium-ionophore and CsA treatment. In V2D1 tumour cells, sensitivity to CsA required additional nucleotides flanking these pentamers. Our data suggest that IL-3 mRNA stabilization by either calcium-dependent or oncogenic pathways involves different intracellular mechanisms.
Wyss
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Institute for Medical Microbiology, University of Basel, Switzerland.
Moroni
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C
D020413:3' Untranslated Regions / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002118:Calcium / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016572:Cyclosporine / Q000494:pharmacology; D007377:Interleukin-3 / Q000235:genetics*; D015759:Ionomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D007377:Interleukin-3; D012333:RNA, Messenger; D015759:Ionomycin; D016572:Cyclosporine; D002118:Calcium