The Translational Landscape of the Human Heart
2019 | journal article; research paper
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Cite this publication
The Translational Landscape of the Human Heart
van Heesch, S.; Witte, F.; Schneider-Lunitz, V.; Schulz, J. F; Adami, E.; Faber, A. B. & Kirchner, M. et al. (2019)
Cell, 178(1) pp. 242.e29-260.e29. DOI: https://doi.org/10.1016/j.cell.2019.05.010
Documents & Media
Details
- Authors
- van Heesch, Sebastiaan; Witte, Franziska; Schneider-Lunitz, Valentin; Schulz, Jana F; Adami, Eleonora; Faber, Allison B.; Kirchner, Marieluise; Maatz, Henrike; Blachut, Susanne; Sandmann, Clara-Louisa; Kanda, Masatoshi; Worth, Catherine L.; Schafer, Sebastian; Calviello, Lorenzo; Merriott, Rhys; Patone, Giannino; Hummel, Oliver; Wyler, Emanuel; Obermayer, Benedikt; Mücke, Michael B.; Lindberg, Eric L.; Trnka, Franziska; Memczak, Sebastian; Schilling, Marcel; Felkin, Leanne E.; Barton, Paul J. R.; Quaife, Nicholas M.; Vanezis, Konstantinos; Diecke, Sebastian; Mukai, Masaya; Mah, Nancy; Oh, Su-Jun; Kurtz, Andreas; Schramm, Christoph; Schwinge, Dorothee; Sebode, Marcial; Harakalova, Magdalena; Asselbergs, Folkert W.; Vink, Aryan; de Weger, Roel A.; Viswanathan, Sivakumar; Widjaja, Anissa A.; Gärtner-Rommel, Anna; Milting, Hendrik; Dos Remedios, Cris; Knosalla, Christoph; Mertins, Philipp; Landthaler, Markus; Vingron, Martin; Linke, Wolfgang A. ; Seidman, Jonathan G.; Seidman, Christine E.; Rajewsky, Nikolaus; Ohler, Uwe; Cook, Stuart A.; Hubner, Norbert
- Abstract
- 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.
- Issue Date
- 2019
- Journal
- Cell
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie - Working Group
- RG Linke (Kardiovaskuläre Physiologie)
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English