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The Translational Landscape of the Human Heart

van Heesch, S; Witte, F; Schneider-Lunitz, V; Schulz, JF; Adami, E; Faber, AB; Kirchner, M; ... Hubner, N; + view all (2019) The Translational Landscape of the Human Heart. Cell , 178 (1) 242-260.e29. 10.1016/j.cell.2019.05.010. Green open access

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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.

Type: Article
Title: The Translational Landscape of the Human Heart
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2019.05.010
Publisher version: https://doi.org/10.1016/j.cell.2019.05.010
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Ribosome profiling, human heart, translatome, translational regulation, heart failure, dilated cardiomyopathy, ORF detection, short ORFs, microproteins, lncRNAs, circRNAs, titin, protein truncating variants
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/10088515
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