title: The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease.
abstract: 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. Together, these yielded 1,148 RBPs, 391 of which are shared with all 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 in evidence of both, mutual exclusivity of, or compatibility between RNA binding and enzymatic function. Our findings raise the prospect of previously hidden RNA-mediated regulatory interactions among cardiomyocyte gene expression, physiology, and metabolism.
authors.affiliation: EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra) ACT 2601, Australia.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Castello
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leicht
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Föehr
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Frese
authors.affiliation: EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra) ACT 2601, Australia.
authors.forename: Chikako
authors.initials: C
authors.lastname: Ragan
authors.affiliation: EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra) ACT 2601, Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kurscheid
authors.affiliation: EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra) ACT 2601, Australia.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Pagler
authors.affiliation: EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra) ACT 2601, Australia.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Krijgsveld
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
authors.affiliation: EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), The Australian National University, Acton (Canberra) ACT 2601, Australia; Victor Chang Cardiac Research Institute, Darlinghurst (Sydney), NSW 2010, Australia. Electronic address: thomas.preiss@anu.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Preiss
mesh_terms: D045744:Cell Line, Tumor; D006367:HeLa Cells; D006331:Heart Diseases / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D020543:Proteome; D012333:RNA, Messenger; D016601:RNA-Binding Proteins