Journal
CELL
Volume 178, Issue 1, Pages 242-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.05.010
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Funding
- EMBO long-term fellowship [ALTF 186-2015, LTFCOFUND2013, GA-2013-609409]
- ERC advanced grant under the European Union Horizon 2020 Research and Innovation Program [AdG788970]
- Leducq Foundation [16CVD03]
- Federal Ministry of Education and Research of Germany [031L0075A]
- German Research Foundation [SFB1002, TPA08]
- British Heart Foundation
- Medical Research Council (UK)
- NIHR Imperial College Biomedical Research Centre
- NIHR Cardiovascular BRU of Royal Brompton & Harefield NHS Foundation Trust UK
- Imperial College Academic Health Science Centre
- Heart Research UK
- Alexander von Humboldt Foundation
- German Federal Ministry of Education and Research of RNA Bioinformatics Center of the German Network for Bioinformatics Infrastructure (de. NBI) [BMBF 031 A538C]
- MRC [MC_U120085815] Funding Source: UKRI
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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 IncRNAs 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 IncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology.
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