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Abstract 13455: Translational Control of Y-Box Binding Protein 1 (Yb-1) During Pathological Cardiac Hypertrophy

Varma, A, Eshita ; Burghaus, A, Jana ; Riechert, A, Eva ; Katus, A, Hugo ; Völkers, A, Mirko

Circulation, 2018, Vol.138(Suppl_1 Suppl 1), pp.A13455-A13455 [Peer Reviewed Journal]

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  • Title:
    Abstract 13455: Translational Control of Y-Box Binding Protein 1 (Yb-1) During Pathological Cardiac Hypertrophy
  • Author: Varma, A, Eshita ; Burghaus, A, Jana ; Riechert, A, Eva ; Katus, A, Hugo ; Völkers, A, Mirko
  • Is Part Of: Circulation, 2018, Vol.138(Suppl_1 Suppl 1), pp.A13455-A13455
  • Description: Background: Cardiac dysfunction is typically associated with altered signal transduction pathways in cardiac myocytes, affecting both gene and protein expression. The control of the protein expression happens on a transcriptional and translational level. RNA binding proteins (RBPs) are an emerging group of post-transcriptional regulators. They are responsible for controlling tissue-specific gene expression by regulating splicing, mRNA stability, translation, and polyadenylation, but the specific role of RBPs in controlling protein expression in the diseased myocardium is still not completely understood.Results: Previous results suggested a critical role of the mechanistic target of rapamycin (mTOR) signalling pathway in the diseased myocardium. Initial experiments done by our group using ribosomal sequencing in mice identified hundreds of mTOR-dependent translationally regulated transcripts in response to transverse aortic constriction (TAC) surgery. This allowed us to identify RNA binding proteins that mediate translational control during pathological growth and are also involved in mTOR signalling pathway. Our results showed YB-1 to be one such RNA binding protein that is up-regulated only in pathological hypertrophy. YB-1 was up-regulated already after hours at the protein level in mice during pathological hypertrophy. Experiments in isolated cardiomyocytes showed that YB-1 depletion prevents cellular growth in vitro by inhibiting protein translation, suggesting that translational controlled expression of YB-1 is necessary for the increase in protein synthesis and cellular growth. Translational control of YB-1 expression is dependent on mTOR signalling and independent by mRNA transcription. Adenoviral overexpression of YB-1 affects cellular size and survival in cardiomyocytes by regulation of protein synthesis. We generated in vivo loss of/gain of models to elucidate the in vivo function of YBX-1. Current experiments are aimed to identify mRNAs bound to YB-1 during cellular growth to define the network of translational controlled transcripts.Conclusion: Our experiments with cardiomyocytes have provided evidence that YB-1 regulated growth response in cardiac myocytes. Importantly, the expression of YB-1 is regulated at a translational level in cardiomyocytes. Since YB-1 is an RNA binding protein, therefore identifying its binding partners will help understand the potential targets in pathological hypertrophic cardiac remodelling.
  • Identifier: ISSN: 0009-7322

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