Retinoic acid receptor‐α regulates synthetic events in human platelets. (1st November 2017)

• Record Type: Journal Article
• Authors: Schwertz, H.; Rowley, J. W.; Zimmerman, G. A.; Weyrich, A. S.; Rondina, M. T.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 15:Number 12(2017)
• Page Start: 2408
• Page End: 2418
• Publication Date: 2017-11-01
• Subjects: blood platelets -- mRNA translation -- protein biosynthesis -- retinoic acid receptors -- translation; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13861
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : 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 MAP1LCB2 mRNA, 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.