The translational landscape of the human heart
File(s)vanHeesch_etal_ 2019.pdf (649.84 KB)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2019-06-27
Date Acceptance
2019-05-06
Citation
Cell, 2019, 178 (1), pp.242-260.e29
ISSN
0092-8674
Publisher
Elsevier BV
Start Page
242
End Page
260.e29
Journal / Book Title
Cell
Volume
178
Issue
1
Copyright Statement
© 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Royal Brompton & Harefield NHS Foundation Trust
Heart Research UK
Fondation Leducq
Imperial College Healthcare NHS Trust- BRC Funding
Fondation Leducq
Fondation Leducq
Imper
Grant Number
N/A
RG2657/17/19
16CVD03
RDB02
11 CVD-01
11 CVD-01
Imperial College London
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
LONG NONCODING RNA
OPEN READING FRAMES
SUBCELLULAR-LOCALIZATION
DIFFERENTIAL TRANSLATION
DILATED CARDIOMYOPATHY
REGULATORY VARIATION
CODON READTHROUGH
TERMINATION
PEPTIDES
CLASSIFICATION
ORF detection
circRNAs
dilated cardiomyopathy
heart failure
human heart
lncRNAs
microproteins
protein-truncating variants
ribosome profiling
short ORFs
titin
translational regulation
translatome
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status
Published
Date Publish Online
2019-05-30