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Anupama Rao_Dissertation.pdf (17.09 MB)

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Elucidating the Role of Translation Initiation Factor, eif41c in Cardiac Development and Regeneration in Zebrafish

Rao, Anupama Shrikant
http://rave.ohiolink.edu/etdc/view?acc_num=osu1692482381639383

Abstract Details

2023, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
Cardiovascular disease is the leading cause of death worldwide, partly because humans lack appreciable capacity to repair or replenish lost or damaged cardiac tissue. 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 determining transcriptional changes occurring during this process. However, comparison of protein levels verses mRNA abundance shows 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 suggesting an important role for post-transcriptional regulation. Here, we describe a new family of translation factors called Eif4e1c which are related to canonical Eif4e proteins that initiate the rate limiting step of mRNA translation by binding to the 5’ mRNA cap. Zebrafish mutants 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 Eif4e proteins with a core group of 23 amino acids retained from ray-finned fish to sharks across ~480 million years. Interestingly, the Eif4e1c family is 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.
Joseph Goldman (Advisor)
Amanda Bird (Committee Member)
Jill Rafael-Fortney (Committee Member)
Sharon Amacher (Committee Member)
178 p.
Cellular Biology; Developmental Biology; Molecular Biology
Zebrafish; Heart Regeneration; Translation initiation factor; Translation regulation; Cardiomyocytes; Eif4e1c

Recommended Citations

Citations

  • Rao, A. S. (2023). Elucidating the Role of Translation Initiation Factor, eif41c in Cardiac Development and Regeneration in Zebrafish [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1692482381639383

    APA Style (7th edition)

  • Rao, Anupama. Elucidating the Role of Translation Initiation Factor, eif41c in Cardiac Development and Regeneration in Zebrafish. 2023. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1692482381639383.

    MLA Style (8th edition)

  • Rao, Anupama. "Elucidating the Role of Translation Initiation Factor, eif41c in Cardiac Development and Regeneration in Zebrafish." Doctoral dissertation, Ohio State University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=osu1692482381639383

    Chicago Manual of Style (17th edition)

osu1692482381639383
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© 2023, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.