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Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition

Brown, Andrew S.
http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957

Abstract Details

2015, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Protein translational regulation by RNA binding proteins (RBPs) is a critical process in maintaining homeostasis. Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells de-differentiate and become mesenchymal, increasing the propensity toward tumorigenesis and/or metastasis. We have identified a heterogeneous nuclear riboprotein E1 (hnRNP E1)-mediated post-transcriptional operon that controls transcript-selective translational regulation of epithelial / mesenchymal transition (EMT)-associated genes. In this regulatory mechanism, hnRNPE1 binds to the 3’-UTR of select transcripts and silences their translation. TGFß reverses translational silencing through Akt2-dependent phosphorylation of hnRNP E1 at Ser-43, resulting in loss of hnRNP E1 binding to RNA. We have identified approximately forty pro-EMT / metastatic mRNAs that are regulated by this hnRNP E1 operon and our preliminary studies have revealed a short stretch of nucleic acids, that we have termed the BAT element (TGF-beta activated translational (BAT) element), present in their respective 3’-UTRs that may be responsible for hnRNP E1 binding. Herein, through the use of in-vitro and in-vivo assays, we demonstrate the contribution of BAT element mutations and constitutively high levels of pSer43 hnRNP E1 to cancer tumorigenesis and metastasis.
Philip Howe, Ph.D. (Advisor)
Derek Damron, Ph.D. (Committee Member)
Srinivasan Vijayaraghavan, Ph.D. (Committee Member)
Olena Piontkivska, Ph.D. (Committee Member)
Bidyut Mohanty, Ph.D. (Committee Member)
138 p.
Bioinformatics; Biology; Biomedical Research; Biostatistics
Cancer Metastasis; RNA Binding Proteins; RNA; Computational Biology; EMT; TGF-beta; Exonuclease Digestion

Recommended Citations

Citations

  • Brown, A. S. (2015). Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957

    APA Style (7th edition)

  • Brown, Andrew. Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition. 2015. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957.

    MLA Style (8th edition)

  • Brown, Andrew. "Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition." Doctoral dissertation, Kent State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957

    Chicago Manual of Style (17th edition)

kent1437943957
518
© 2015, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.