The translational landscape of the human heart

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Item Type:	Article
Title:	The translational landscape of the human heart
Creators Name:	van Heesch, S., Witte, F., Schneider-Lunitz, V., Schulz, J.F., Adami, E., Faber, A., Kirchner, M., Maatz, H., Blachut, S., Sandmann, C.L., Kanda, M., Worth, C.L., Schafer, S., Calviello, L., Merriott, R., Patone, G., Hummel, O., Wyler, E., Obermayer, B., Mücke, M., Lindberg, E.L., Trnka, F., Memczak, S., Schilling, M., Felkin, L.E., Barton, P.J.R., Quaife, N.M., Vanezis, K., Diecke, S., Mukai, M., Mah, N., Oh, S.J., Kurtz, A., Schramm, C., Schwinge, D., Sebode, M., Harakalova, M., Asselbergs, F.W., Vink, A., de Weger, R.A., Viswanathan, S., Widjaja, A.A., Gärtner-Rommel, A., Milting, H., Dos Remedios, C., Knosalla, C., Mertins, P., Landthaler, M., Vingron, M., Linke, W.A., Seidman, J.G., Seidman, C.E., Rajewsky, N., Ohler, U., Cook, S.A. and Hubner, N.
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.
Keywords:	Ribosome Profiling, Human Heart, Translatome, Translational Regulation, Heart Failure, Dilated Cardiomyopathy, ORF Detection, Short ORFs, Microproteins, lncRNAs, circRNAs, Titin, Protein-Truncating Variants, Animal, Mice, Rats
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	178
Number:	1
Page Range:	242-260
Date:	27 June 2019
Additional Information:	Copyright © 2019 Elsevier Ltd. All rights reserved.
Official Publication:	https://doi.org/10.1016/j.cell.2019.05.010
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