The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease — ASN Events

The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease (#118)

Yalin Liao 1 , Alfredo Castello 2 3 , Bernd Fischer 2 4 , Stefan Leicht 2 , Sophia Föehr 2 , Christian K Frese 2 , Chikako Ragan 1 , Sebastian Kurscheid 1 , Eloisa Pagler 1 , Hao Yang 1 , Jeroen Krijgsveld 2 4 , Matthias W Hentze 2 , Thomas Preiss 1 5
  1. JCSMR, The Australian National University, Acton (Canberra), ACT, Australia
  2. European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
  3. Department of Biochemistry, Oxford University, Oxford, United Kindom
  4. German Cancer Research Centre, Heidelberg, Germany
  5. Victor Chang Cardiac Research Institute, Sydney, NSW, Australia

RNA functions, through the dynamic formation of complexes with RNA-binding proteins (RBPs) in all clades of life. We determined the RBP repertoire of beating cardiomyocytic HL-1 cells, by jointly employing two in vivo proteomic methods, mRNA interactome capture and RBDmap (Castello et al., 2016). Together, these yielded 1148 RBPs, 391 of which are shared with other available mammalian RBP repertoires, while 393 are thus far unique to cardiomyocytes. RBDmap, further identified 568 regions of RNA contact within 368 RBPs. The cardiomyocyte mRNA interactome composition reflects their unique biology. Proteins with roles in cardiovascular physiology or disease, mitochondrial function and intermediary metabolism are all highly represented. Notably, we identified 73 metabolic enzymes as RBPs. RNA-enzyme contacts frequently involve Rossmann fold domains with examples of both, mutual exclusivity of, or compatibility between, RNA-binding and enzymatic function in evidence. Our findings raise the prospect of previously hidden RNA-mediated regulatory interactions between cardiomyocyte gene expression, physiology and metabolism (Liao et al., 2016).

  1. Liao Y, Castello A, Fischer B, Leicht S, Föehr S, Frese CK, Ragan C, Kurscheid S, Pagler E, Yang H, Krijgsveld J, Hentze MW, Preiss T. The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease. Cell Reports. 2016 Aug 2;16(5):1456-69.
  2. Castello A, Fischer B, Frese CK, Horos R, Alleaume AM, Foehr S, Curk T, Krijgsveld J, Hentze MW. Comprehensive Identification of RNA-Binding Domains in Human Cells. Molecular Cell. 2016 Aug 18;63(4):696-710.
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