IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability
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Author(s)
Ernst, Jason
Ghanem, Louis
Bar-Joseph, Ziv
McNamara, Michael
Brown, Jason
Steinman, Richard A.
Date Issued
October 2009
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Ernst J, Ghanem L, Bar-Joseph Z, McNamara M, Brown J, et al. 2009 IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Altering mRNA Stability. PLoS ONE 4(10): e7469. doi:10.1371/journal.pone.0007469
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Final published version
Abstract
The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and
stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth
through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely
unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating
that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function.
Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6
(IL-6) 39-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized
transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay
turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/
Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant
stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
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DOI of Published Version
http://dx.doi.org/10.1371/journal.pone.0007469
