Activated polymorphonuclear leukocytes rapidly synthesize retinoic acid receptor-alpha: a mechanism for translational control of transcriptional events

In addition to releasing preformed granular proteins, polymorphonuclear leukocytes (PMNs) synthesize chemokines and other factors under transcriptional control. Here we demonstrate that PMNs express an inducible transcriptional modulator by signal-dependent activation of specialized mechanisms that...

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Bibliographic Details
Published in:The Journal of experimental medicine 2004-09, Vol.200 (5), p.671-680
Main Authors: Yost, Christian C, Denis, Melvin M, Lindemann, Stephan, Rubner, Frederick J, Marathe, Gopal K, Buerke, Michael, McIntyre, Thomas M, Weyrich, Andrew S, Zimmerman, Guy A
Format: Article
Language:English
Subjects:
5' Untranslated Regions
Cell Differentiation
DNA, Complementary - metabolism
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation
HL-60 Cells
Humans
Interleukin-8 - metabolism
Models, Molecular
Neutrophils - metabolism
Oligonucleotide Array Sequence Analysis
Polyribosomes - metabolism
Protein Biosynthesis
Protein Structure, Secondary
Receptors, Retinoic Acid - biosynthesis
Retinoic Acid Receptor alpha
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Time Factors
Transcription, Genetic
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Summary:In addition to releasing preformed granular proteins, polymorphonuclear leukocytes (PMNs) synthesize chemokines and other factors under transcriptional control. Here we demonstrate that PMNs express an inducible transcriptional modulator by signal-dependent activation of specialized mechanisms that regulate messenger RNA (mRNA) translation. HL-60 myelocytic cells differentiated to surrogate PMNs respond to activation by platelet activating factor by initiating translation and with appearance of specific mRNA transcripts in polyribosomes. cDNA array analysis of the polyribosome fraction demonstrated that retinoic acid receptor (RAR)-alpha, a transcription factor that controls the expression of multiple genes, is one of the polyribosome-associated transcripts. Quiescent surrogate HL60 PMNs and primary human PMNs contain constitutive message for RAR-alpha but little or no protein. RAR-alpha protein is rapidly synthesized in response to platelet activating factor under the control of a specialized translational regulator, mammalian target of rapamycin, and is blocked by the therapeutic macrolide rapamycin, events consistent with features of the 5' untranslated region of the transcript. Newly synthesized RAR-alpha modulates production of interleukin-8. Rapid expression of a transcription factor under translational control is a previously unrecognized mechanism in human PMNs that indicates unexpected diversity in gene regulation in this critical innate immune effector cell.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20040224