| Literature DB >> 31155234 |
Sebastiaan van Heesch1, Franziska Witte2, Valentin Schneider-Lunitz2, Jana F Schulz2, Eleonora Adami3, Allison B Faber2, Marieluise Kirchner4, Henrike Maatz2, Susanne Blachut2, Clara-Louisa Sandmann2, Masatoshi Kanda2, Catherine L Worth2, Sebastian Schafer5, Lorenzo Calviello6, Rhys Merriott2, Giannino Patone2, Oliver Hummel2, Emanuel Wyler7, Benedikt Obermayer8, Michael B Mücke2, Eric L Lindberg2, Franziska Trnka2, Sebastian Memczak7, Marcel Schilling7, Leanne E Felkin9, Paul J R Barton9, Nicholas M Quaife10, Konstantinos Vanezis11, Sebastian Diecke12, Masaya Mukai13, Nancy Mah14, Su-Jun Oh14, Andreas Kurtz14, Christoph Schramm15, Dorothee Schwinge16, Marcial Sebode16, Magdalena Harakalova17, Folkert W Asselbergs18, Aryan Vink19, Roel A de Weger19, Sivakumar Viswanathan20, Anissa A Widjaja20, Anna Gärtner-Rommel21, Hendrik Milting21, Cris Dos Remedios22, Christoph Knosalla23, Philipp Mertins4, Markus Landthaler24, Martin Vingron25, Wolfgang A Linke26, Jonathan G Seidman27, Christine E Seidman28, Nikolaus Rajewsky7, Uwe Ohler6, Stuart A Cook29, Norbert Hubner30.
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.Entities:
Keywords: ORF detection; circRNAs; dilated cardiomyopathy; heart failure; human heart; lncRNAs; microproteins; protein-truncating variants; ribosome profiling; short ORFs; titin; translational regulation; translatome
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Year: 2019 PMID： 31155234 DOI： 10.1016/j.cell.2019.05.010
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582