The Translational Landscape of the Human Heart

Cell 178, 1–19, June 27, 2019 ª 2019 Elsevier Inc.
Authors
Sebastiaan van Heesch, Franziska Witte, Valentin Schneider-Lunitz, Jana F. Schulz,Eleonora Adami, Allison B. Faber, Marieluise Kirchner, Henrike Maatz, Susanne Blachut, Clara-Louisa Sandmann, Masatoshi Kanda,1Catherine L. Worth,1 Sebastian Schafer,2,4 Lorenzo Calviello,5,6,33 Rhys Merriott,1 Giannino Patone,1 Oliver Hummel,1Emanuel Wyler,5 Benedikt Obermayer,5,7 Michael B. Mu¨ cke,1 Eric L. Lindberg,1 Franziska Trnka,1 Sebastian Memczak,5,36
Marcel Schilling,5 Leanne E. Felkin,8,9 Paul J.R. Barton,8,9 Nicholas M. Quaife,8,9,32 Konstantinos Vanezis,9,32, Sebastian Diecke,10,11,12 Masaya Mukai,13 Nancy Mah,14 Su-Jun Oh,14 Andreas Kurtz,14 Christoph Schramm,15,16, Dorothee Schwinge,16 Marcial Sebode,16 Magdalena Harakalova,17,18 Folkert W. Asselbergs,17,19,20 Aryan Vink,18, Roel A. de Weger,18 Sivakumar Viswanathan,2 Anissa A. Widjaja,2 Anna Ga¨rtner-Rommel,21 Hendrik Milting,21, Cris dos Remedios,22 Christoph Knosalla,11,23,24 Philipp Mertins,3 Markus Landthaler,5,25 Martin Vingron,26, Wolfgang A. Linke,27,28 Jonathan G. Seidman,29 Christine E. Seidman,29,30,31 Nikolaus Rajewsky,5 Uwe Ohler,5,6, Stuart A. Cook,2,4,9,32 and Norbert Hubner1,11,12,24,35,37,*
06-19-2019 HSW1057
12:00pm
PST
Categories
Long Noncoding RNAs & Circular RNAs
Speaker
Elizabeth Crouch
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 proteintruncating 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.