Poster abstracts

Poster number 25 submitted by Anupama Rao

Changes in Translation Drive Heart Growth During Development and Regeneration in Zebrafish.

Anupama Rao (Molecular, Cellular, and Developmental Biology), Joseph Aaron Goldman (Biochemistry and Pharmacology)

Abstract:
Acute myocardial infarction (MI) is the leading cause of death in today’s world. The mammalian heart lacks appreciable capacity to regenerate the tissue lost due to MI leaving the patients vulnerable to heart failure. However, zebrafish can regenerate large portions of cardiac tissues lost as a result of injury. Many studies have surveyed epigenetic, genomic and transcriptional changes to yield important insights into cardiac regeneration, identifying many required factors in the process. Here, we show that changes in translation also play an important role in driving cardiac regeneration. Using ribosome profiling we documented the changes in translation efficiency that accompany heart regeneration and identified thousands of transcripts that change in their association with ribosomes. Specific components of the translational machinery may be critical for regulation of translation of these transcripts. We observed transcriptional upregulation of translation initiation factors, one of which is eif4e1c which is known to bind 5’ methylated caps. eIF4E acts as the limiting factor in the translation initiation, and its expression levels help determine the occurrence of mRNA translation. We deleted eif4e1c using CRISPR and observed lower survival rates and overall growth deficits. We also showed that eif4e1c is required for efficient proliferation of cardiomyocytes (CMs) in the zebrafish hearts during normal growth and during regeneration. The findings of this study support a model of cardiac regeneration in which regulation of gene expression through translation is a critical component driving CM proliferation. We identified the translation initiation factor, eif4e1c and its role during zebrafish development and regeneration.

Keywords: Cardiac regeneration, Translation, Zebrafish