Poster abstracts
Poster number 33 submitted by Anupama Rao
Changes in Translation Drive Heart Growth During Development and Regeneration in Zebrafish.
Anupama Rao (Department of Biological Chemistry and Pharmacology, The Ohio State University), Baken Lyu (Department of Biological Chemistry and Pharmacology, The Ohio State University), Ariel Bazzini (Stowers Institute), Antonio Giraldez (Yale University), Kenneth Poss (Duke University School of Medicine), Joseph Aaron Goldman (Department of Biological Chemistry and Pharmacology, The Ohio State University)
Abstract:
Heart disease is the leading cause of death in today’s world. Heart disease patients are prone to heart damage and subsequent loss of cardiac tissue. The mammalian heart lacks appreciable capacity to regenerate this lost tissue leaving the patients vulnerable to heart failure. However, zebrafish can regenerate large portions of cardiac tissues lost following 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. There is transcriptional upregulation of translation initiation factors during regeneration, 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. Here, we identified the translation initiation factor, eif4e1c and its role during zebrafish development and regeneration. Deletion of eif4e1c using CRISPR resulted in lower survival rates to adulthood after normal development although with overall growth deficits. Furthermore, eif4e1c is required for efficient proliferation of cardiomyocytes (CMs) in zebrafish hearts during normal growth and during regeneration. In sum, 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.
Keywords: Cardiac regeneration, Translation, Zebrafish