SRA

These human cell line, mice and rat data belong to a study that additionally comprises of 80 human cardiac translatomes. The human data have been submitted to the European Genome-Phenome Archive, ega-archive.org , EGA. The accession number for the human data is EGAS00001003263 and access is restricted and depends on a finalised Data Access Agreement, DAA. Furthermore, all study/publication related proteomics data have been deposited to the ProteomeXchange (PRIDE) repository, under accession PXD012593 . The regulation of gene expression in human tissues is incompletely understood and has primarily been studied on the transcriptional level. Here, we quantify the impact of translation on gene expression and annotate novel translational events in 80 human hearts. These include 65 patients with dilated cardiomyopathy (DCM) – the most common cause of heart transplantation – and 15 unaffected controls. We show that translational regulation modulates disease-associated molecular processes. Moreover, ribosome dynamics at protein truncating variants reveal incomplete termination of translation at DCM-causing titin-truncating variants. Finally, we identify dozens of unknown microproteins translated from lncRNAs and circRNAs and link these to mitochondrial processes. Several microproteins are expressed from lncRNAs with previously demonstrated function, suggesting a dual coding and noncoding role. This resource will stimulate novel functional investigations into human health and disease and may serve as a blueprint for characterizing the translational landscape of other human tissues.