Talk abstracts
Talk on Tuesday 09:45-10:00am submitted by Anupama Rao
A Fish Specific Translation Initiation Factor, Eif4e1c Regulates Cardiac Growth and Metabolism During Development and Regeneration.
Anupama Rao (Molecular, Cellular, and Developmental Biology,The Ohio State University), Baken Lyu, Ishrat Jahan, Anna Lubertozzi (Department of Biological Chemistry and Pharmacology, The Ohio State University), Frank Tedeschi, Eckhard Jankowsky, Gao Zhou (Center for RNA Molecular Biology, Department of Biochemistry, School of Medicine, Case Western Reserve University), Bryan Carstens (Department of Evolution, Ecology, and Organismal Biology, The Ohio State University), Kenneth Poss (Duke Regeneration Center, Duke University School of Medicine), Kedryn Baskin (Department of Cell Biology and Physiology, The Ohio State University Medical Center)
Abstract:
Unlike mammals, adult zebrafish have a remarkable ability to regenerate large portions of cardiac tissues lost following injury. Most studies on zebrafish heart regeneration have focused on transcription; yet, comparison of protein levels verses mRNA abundance show that mRNA expression accounts for just 40% of the protein product. Only a minority of proteins changing in abundance during heart regeneration correlate with the amount of mRNA. This suggests an important role for post-transcriptional regulation. Here, we describe a new family of translation factors called Eif4e1c which are related to canonical proteins that initiate the rate limiting step of mRNA translation. Zebrafish mutant for eif4e1c have fewer cardiomyocytes and have reduced proliferation of heart muscle after injury. Additionally, eif4e1c mutants show widespread translational dysregulation of mRNA and metabolic changes in their hearts. Eif4e1c is more conserved throughout evolution than the canonical proteins with a core group of 23 amino acids retained from ray-finned fish to sharks across ~480 million years. Interestingly, the Eif4e1c family was lost in amphibians and is absent from all terrestrial species. To our knowledge this makes eif4e1c the only fish specific gene with described roles in heart regeneration. In sum, we show that eif4e1c is critical for development and regeneration of zebrafish hearts revealing context-dependent requirements by translation initiation regulators during heart regeneration.
References:
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Goldman, J. A., Kuzu, G., Lee, N., Karasik, J., Gemberling, M., Foglia, M. J., Karra, R., Dickson, A. L., Sun, F., Tolstorukov, M. Y., et al. (2017). Resolving Heart Regeneration by Replacement Histone Profiling. Dev Cell 40, 392 404.e5.
Keywords: Heart regeneration, Translation regulation, Zebrafish development