The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease

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 1,14...

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Main Authors: Castello, A, Liao, Y, Fischer, B, Leicht, S, Föehr, S, Frese, C, Ragan, C, Kurscheid, S, Pagler, E, Yang, H, Krijgsveld, J, Hentze, M, Preiss, T
פורמט: Journal article
יצא לאור: Cell Press 2016
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author Castello, A
Liao, Y
Fischer, B
Leicht, S
Föehr, S
Frese, C
Ragan, C
Kurscheid, S
Pagler, E
Yang, H
Krijgsveld, J
Hentze, M
Preiss, T
author_facet Castello, A
Liao, Y
Fischer, B
Leicht, S
Föehr, S
Frese, C
Ragan, C
Kurscheid, S
Pagler, E
Yang, H
Krijgsveld, J
Hentze, M
Preiss, T
author_sort Castello, A
collection OXFORD
description 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.
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spelling oxford-uuid:8dcddb05-fc25-4b96-97d9-4ab76eee03ef2022-03-26T22:53:31ZThe cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8dcddb05-fc25-4b96-97d9-4ab76eee03efSymplectic Elements at OxfordCell Press2016Castello, ALiao, YFischer, BLeicht, SFöehr, SFrese, CRagan, CKurscheid, SPagler, EYang, HKrijgsveld, JHentze, MPreiss, TRNA 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.
spellingShingle Castello, A
Liao, Y
Fischer, B
Leicht, S
Föehr, S
Frese, C
Ragan, C
Kurscheid, S
Pagler, E
Yang, H
Krijgsveld, J
Hentze, M
Preiss, T
The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease
title The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease
title_full The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease
title_fullStr The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease
title_full_unstemmed The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease
title_short The cardiomyocyte RNA-binding proteome: links to intermediary metabolism and heart disease
title_sort cardiomyocyte rna binding proteome links to intermediary metabolism and heart disease
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