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The translational landscape of the human heart

Item Type:Article
Title:The translational landscape of the human heart
Creators Name:van Heesch, S. and Witte, F. and Schneider-Lunitz, V. and Schulz, J.F. and Adami, E. and Faber, A. and Kirchner, M. and Maatz, H. and Blachut, S. and Sandmann, C.L. and Kanda, M. and Worth, C.L. and Schafer, S. and Calviello, L. and Merriott, R. and Patone, G. and Hummel, O. and Wyler, E. and Obermayer, B. and Mücke, M.B. and Lindberg, E.L. and Trnka, F. and Memczak, S. and Schilling, M. and Felkin, L.E. and Barton, P.J.R. and Quaife, N.M. and Vanezis, K. and Diecke, S. and Mukai, M. and Mah, N. and Oh, S.J. and Kurtz, A. and Schramm, C. and Schwinge, D. and Sebode, M. and Harakalova, M. and Asselbergs, F.W. and Vink, A. and de Weger, R.A. and Viswanathan, S. and Widjaja, A.A. and Gärtner-Rommel, A. and Milting, H. and Dos Remedios, C. and Knosalla, C. and Mertins, P. and Landthaler, M. and Vingron, M. and Linke, W.A. and Seidman, J.G. and Seidman, C.E. and Rajewsky, N. and Ohler, U. and 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
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:178
Number:1
Page Range:242-260
Date:27 June 2019
Official Publication:https://doi.org/10.1016/j.cell.2019.05.010
PubMed:View item in PubMed

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