The Translational Landscape of the Human Heart.

Adolescent Adult Aged Animals Codon / genetics Female Gene Expression Regulation HEK293 Cells Humans Infant Male Mice Mice, Inbred C57BL Middle Aged Myocardium / metabolism Open Reading Frames / genetics Protein Biosynthesis RNA, Circular / genetics RNA, Long Noncoding / genetics RNA, Messenger / genetics Rats Ribosomes / genetics Young Adult
ORF detection circRNAs dilated cardiomyopathy heart failure human heart lncRNAs microproteins protein-truncating variants ribosome profiling short ORFs titin translational regulation translatome

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
27 06 2019
Historique:
received: 05 11 2018
revised: 01 03 2019
accepted: 06 05 2019
pubmed: 4 6 2019
medline: 9 4 2020
entrez: 4 6 2019
Statut: ppublish

Résumé

Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, suggesting inefficient translation termination. We identify hundreds of previously undetected microproteins, expressed from lncRNAs and circRNAs, for which we validate the protein products in vivo. The translation of microproteins is not restricted to the heart and prominent in the translatomes of human kidney and liver. We associate these microproteins with diverse cellular processes and compartments and find that many locate to the mitochondria. Importantly, dozens of microproteins are translated from lncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology.

Identifiants

DOI: 10.1016/j.cell.2019.05.010 PMID: 31155234
pubmed: 31155234
pii: S0092-8674(19)30508-2
doi: 10.1016/j.cell.2019.05.010
pii:
doi:

Substances chimiques

Codon 0
RNA, Circular 0
RNA, Long Noncoding 0
RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

242-260.e29

Subventions

Organisme : Medical Research Council
ID : MC_U120085815
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Sebastiaan van Heesch (S)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany. Electronic address: sebastiaanvanheesch@gmail.com.

Franziska Witte (F)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Valentin Schneider-Lunitz (V)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Jana F Schulz (JF)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Eleonora Adami (E)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore, Singapore 169857, Singapore.

Allison B Faber (AB)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Marieluise Kirchner (M)

Proteomics Platform, Berlin Institute of Health (BIH) and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Henrike Maatz (H)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Susanne Blachut (S)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Clara-Louisa Sandmann (CL)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Masatoshi Kanda (M)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Catherine L Worth (CL)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Sebastian Schafer (S)

Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore, Singapore 169857, Singapore; National Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore 169609, Singapore.

Lorenzo Calviello (L)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany; Department of Biology, Humboldt Universität Berlin, 10099 Berlin, Germany.

Rhys Merriott (R)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Giannino Patone (G)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Oliver Hummel (O)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Emanuel Wyler (E)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany.

Benedikt Obermayer (B)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany; Core Unit Bioinformatics, Berlin Institute of Health (BIH), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité-Universitätsmedizin, 10117 Berlin, Germany.

Michael B Mücke (MB)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Eric L Lindberg (EL)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Franziska Trnka (F)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Sebastian Memczak (S)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany.

Marcel Schilling (M)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany.

Leanne E Felkin (LE)

Cardiovascular Research Centre, Royal Brompton and Harefield NHS Trust, SW3 6NP London, UK; National Heart and Lung Institute, Imperial College London, SW3 6LY London, UK.

Paul J R Barton (PJR)

Cardiovascular Research Centre, Royal Brompton and Harefield NHS Trust, SW3 6NP London, UK; National Heart and Lung Institute, Imperial College London, SW3 6LY London, UK.

Nicholas M Quaife (NM)

Cardiovascular Research Centre, Royal Brompton and Harefield NHS Trust, SW3 6NP London, UK; National Heart and Lung Institute, Imperial College London, SW3 6LY London, UK; MRC-London Institute of Medical Sciences, Hammersmith Hospital Campus, London W12 0NN, UK.

Konstantinos Vanezis (K)

National Heart and Lung Institute, Imperial College London, SW3 6LY London, UK; MRC-London Institute of Medical Sciences, Hammersmith Hospital Campus, London W12 0NN, UK.

Sebastian Diecke (S)

Pluripotent Stem Cells Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany; Berlin Institute of Health (BIH), 10178 Berlin, Germany.

Masaya Mukai (M)

Department of Rheumatology and Clinical Immunology, Sapporo City General Hospital, Sapporo, Hokkaido 060-8604, Japan.

Nancy Mah (N)

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Su-Jun Oh (SJ)

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Andreas Kurtz (A)

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Christoph Schramm (C)

Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; First Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Dorothee Schwinge (D)

First Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Marcial Sebode (M)

First Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Magdalena Harakalova (M)

Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.

Folkert W Asselbergs (FW)

Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, 3511 EP Utrecht, Utrecht, the Netherlands; Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, NW1 2DA London, UK.

Aryan Vink (A)

Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.

Roel A de Weger (RA)

Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.

Sivakumar Viswanathan (S)

Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore, Singapore 169857, Singapore.

Anissa A Widjaja (AA)

Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore, Singapore 169857, Singapore.

Anna Gärtner-Rommel (A)

Herz- und Diabeteszentrum NRW, Universitätsklinikum der Ruhr-Universität, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, 32545 Bad Oeynhausen, Germany.

Hendrik Milting (H)

Herz- und Diabeteszentrum NRW, Universitätsklinikum der Ruhr-Universität, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, 32545 Bad Oeynhausen, Germany.

Cris Dos Remedios (C)

Discipline of Anatomy and Histology, Bosch Institute, Anderson Stuart Building, University of Sydney, Sydney, NSW 2006, Australia.

Christoph Knosalla (C)

DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany.

Philipp Mertins (P)

Proteomics Platform, Berlin Institute of Health (BIH) and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.

Markus Landthaler (M)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany; IRI Life Sciences, Institute für Biologie, Humboldt Universität zu Berlin, 10115 Berlin, Germany.

Martin Vingron (M)

Max Planck Institute for Molecular Genetics, Department of Computational Molecular Biology, 14195 Berlin, Germany.

Wolfgang A Linke (WA)

Institute of Physiology II, University of Münster, 48149 Münster, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, 37075 Göttingen, Germany.

Jonathan G Seidman (JG)

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Christine E Seidman (CE)

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Nikolaus Rajewsky (N)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany.

Uwe Ohler (U)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany; Department of Biology, Humboldt Universität Berlin, 10099 Berlin, Germany.

Stuart A Cook (SA)

Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore, Singapore 169857, Singapore; National Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore 169609, Singapore; National Heart and Lung Institute, Imperial College London, SW3 6LY London, UK; MRC-London Institute of Medical Sciences, Hammersmith Hospital Campus, London W12 0NN, UK.

Norbert Hubner (N)

Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347 Berlin, Germany; Berlin Institute of Health (BIH), 10178 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany. Electronic address: nhuebner@mdc-berlin.de.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Eucaryotes › Animaux › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Codon › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Myocarde › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Cadres ouverts de lecture › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Biosynthèse des protéines › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN circulaire › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › ARN long non codant › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Ribosomes › The Translational Landscape of the Human Heart.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › The Translational Landscape of the Human Heart.