Oct 24, 2018

Translational control of cardiac fibrosis

BioRxiv : the Preprint Server for Biology
Sonia ChothaniOwen JL Rackham

Abstract

Background: Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global post-transcriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. Methods: Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used miRNA- and RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. To reveal post-transcriptional mechanisms in the human fibrotic heart, we then integrated our findings with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients. Results: We generated nucleotide-resolution translatome data during the TGFβ1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation and dynamic variation in ribosome occupancy affects protein abundance indepe...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Specimen Type - Fibroblasts
TGFA protein, human
Post-Transcriptional Regulation
Genes
Pathogenic Organism
Sequence Determinations, RNA
Transcription, Genetic
MBNL2 gene
Transcription, RNA-dependent

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