Retinoic acid receptor‐α regulates synthetic events in human platelets

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...

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Published in:Journal of thrombosis and haemostasis 2017-12, Vol.15 (12), p.2408-2418
Main Authors: Schwertz, H., Rowley, J. W., Zimmerman, G. A., Weyrich, A. S., Rondina, M. T.
Format: Article
Language:English
Subjects:
Angiopoietin-1 - biosynthesis
Angiopoietin-1 - blood
Angiopoietin-1 - genetics
Base Sequence
Binding Sites - genetics
blood platelets
Blood Platelets - drug effects
Blood Platelets - metabolism
Blood Proteins - biosynthesis
Blood Proteins - genetics
Humans
In Vitro Techniques
Microtubule-Associated Proteins - biosynthesis
Microtubule-Associated Proteins - blood
Microtubule-Associated Proteins - genetics
mRNA translation
Protein Biosynthesis
Retinoic Acid Receptor alpha - blood
Retinoic Acid Receptor alpha - genetics
retinoic acid receptors
RNA, Messenger - blood
RNA, Messenger - genetics
translation
Tretinoin - pharmacology
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Summary: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 RARα controls protein translational events in human platelets. Methods Isolated human platelets were treated with the pan‐RAR agonist all‐trans‐retinoic acid (atRA). Global and targeted translational events were examined. Results Stimulation of platelets with atRA significantly increased global protein expression. RARα protein bound to a subset of platelet mRNAs, as measured by next‐generation RNA‐sequencing. In‐depth analyses of 5′ and 3′‐untranslated regions of the RARα‐bound mRNAs revealed consensus RARα binding sites in microtubule‐associated protein 1 light chain 3 beta 2 (MAP1LC3B2), SLAIN motif‐containing protein 2 (SLAIN2) and angiopoietin‐1 (ANGPT1) transcripts. When platelets were treated with atRA, binding interactions between RARα protein and mRNA for MAP1LC3B2, SLAIN2 and ANGPT1 were significantly decreased. Consistent with the release of bound RARα protein from MAP1LCB2mRNA, we observed an increase in the synthesis of MAP1LC3B2 protein. Conclusions These findings provide the first evidence that RARα, a nuclear transcriptional factor, regulates synthetic events in anucleate human platelets. They also reveal an additional non‐genomic role for RARα in platelets that may have implications for the vitamin A‐dependent signaling in humans.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.13861