Open AccessCyclosporin A Promotes Translational Silencing of Autocrine Interleukin-3 via Ribosome-Associated Deadenylation
Author(s) -
Asha P. K. Nair,
Hans H. Hirsch,
Marco Colombi,
Christoph Moroni
Publication year - 1999
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.19.1.889
Subject(s) - biology , gene silencing , microbiology and biotechnology , autocrine signalling , rna interference , genetics , rna , cell culture , gene
Translation is regulated predominantly by an interplay betweencis elements at the 3′ and 5′ ends of mRNAs andtrans -acting proteins. Cyclosporin A (CsA), a calcineurin antagonist and blocker of interleukin-2 (IL-2) transcription in T cells, was found to inhibit translation of IL-3 mRNA in autocrine mast cell tumor lines. The mechanism involved ribosome-associated poly(A) shortening and required an intact AU-rich element in the 3′ untranslated region. FK506, another calcineurin inhibitor, shared the effect. The translational inhibition by CsA was specific to oncogenically induced lymphokines IL-3 and IL-4 but not to IL-6, c-jun, and c-myc, which are expressed in the nonmalignant precursor cells. Furthermore, no translational down-regulation of the mRNA was observed in IL-3-transfected precursor cells. These data suggest that translational silencing is associated with the tumor phenotype.