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Retinoic acid receptor‐α regulates synthetic events in human platelets
Author(s) -
Schwertz H.,
Rowley J. W.,
Zimmerman G. A.,
Weyrich A. S.,
Rondina M. T.
Publication year - 2017
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13861
Subject(s) - retinoic acid , platelet , retinoic acid receptor , receptor , chemistry , microbiology and biotechnology , cancer research , biology , immunology , biochemistry , gene
Essentials Platelets express retinoic acid receptor (RAR)α protein, specifically binding target mRNAs. mRNAs under RARα control include MAP1LC3B2, SLAIN2, and ANGPT1. All‐trans retinoic acid (atRA) releases RARα from its target mRNA. RARα expressed in human platelets exerts translational control via direct mRNA binding.Summary Background Translational control mechanisms in platelets are incompletely defined. Here, we determined whether the nuclear transcription factor RAR α controls protein translational events in human platelets. Methods Isolated human platelets were treated with the pan‐ RAR agonist all‐trans‐retinoic acid (at RA ). Global and targeted translational events were examined. Results Stimulation of platelets with at RA significantly increased global protein expression. RAR α protein bound to a subset of platelet mRNA s, as measured by next‐generation RNA ‐sequencing. In‐depth analyses of 5′ and 3′‐untranslated regions of the RAR α‐bound mRNA s revealed consensus RAR α binding sites in microtubule‐associated protein 1 light chain 3 beta 2 ( MAP 1 LC 3B2), SLAIN motif‐containing protein 2 ( SLAIN 2) and angiopoietin‐1 ( ANGPT 1) transcripts. When platelets were treated with at RA , binding interactions between RAR α protein and mRNA for MAP 1 LC 3B2, SLAIN 2 and ANGPT 1 were significantly decreased. Consistent with the release of bound RAR α protein from MAP 1 LCB 2 mRNA , we observed an increase in the synthesis of MAP 1 LC 3B2 protein. Conclusions These findings provide the first evidence that RAR α, a nuclear transcriptional factor, regulates synthetic events in anucleate human platelets. They also reveal an additional non‐genomic role for RAR α in platelets that may have implications for the vitamin A‐dependent signaling in humans.