| Title: |
The Translational Landscape of the Human Heart |
| Authors: |
van Heesch,Sebastiaan; Witte,Franziska; Schneider-Lunitz,Valentin; Schulz,Jana F; Adami,Eleonora; Faber,Allison B; Kirchner,Marieluise; Maatz,Henrike; Blachut,Susanne; Sandmann,Clara-Louisa; Kanda,Masatoshi; Worth,Catherine L; Schafer,Sebastian; Calviello,Lorenzo; Merriott,Rhys; Patone,Giannino; Hummel,Oliver; Wyler,Emanuel; Obermayer,Benedikt; Mücke,Michael B; Lindberg,Eric L; Trnka,Franziska; Memczak,Sebastian; Schilling,Marcel; Felkin,Leanne E; Barton,Paul J R; Quaife,Nicholas M; Vanezis,Konstantinos; Diecke,Sebastian; Mukai,Masaya; Mah,Nancy; Oh,Su-Jun; Kurtz,Andreas; Schramm,Christoph; Schwinge,Dorothee; Sebode,Marcial; Harakalova, Magdalena; Asselbergs, Folkert W; Vink, Aryan; de Weger, Roel A; Viswanathan,Sivakumar; Widjaja,Anissa A; Gärtner-Rommel,Anna; Milting,Hendrik; Dos Remedios,Cris; Knosalla,Christoph; Mertins,Philipp; Landthaler,Markus; Vingron,Martin; Linke,Wolfgang A; Seidman,Jonathan G; Seidman,Christine E; Rajewsky,Nikolaus; Ohler,Uwe; Cook,Stuart A; Hubner,Norbert; Onderzoek Precision medicine; Team Medisch; Circulatory Health; Pathologie Pathologen staf; Pathologie Moleculair; Cancer |
| Publication Year: |
2019 |
| Subject Terms: |
circRNAs; dilated cardiomyopathy; heart failure; human heart; lncRNAs; microproteins; ORF detection; protein-truncating variants; ribosome profiling; short ORFs; titin; translational regulation; translatome; Taverne; General Biochemistry,Genetics and Molecular Biology; Journal Article |
| Description: |
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. Translational profiling in a primary human tissue reveals frequent translation downstream of predicted disease-causing variants as well as translation of hundreds of microproteins from long noncoding RNAs and circular RNAs. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
0092-8674 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/438905 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/438905 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.C4E6F15D |
| Database: |
BASE |