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

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

Bibliographic Details
Main Author: Brown, Andrew S.
Language:English
Published: Kent State University / OhioLINK 2015
Subjects:
Bioinformatics
Biology
Biomedical Research
Biostatistics
Cancer Metastasis
RNA Binding Proteins
RNA
Computational Biology
EMT
TGF-beta
Exonuclease Digestion
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-kent14379439572021-08-03T06:32:21Z Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition Brown, Andrew S. Bioinformatics Biology Biomedical Research Biostatistics Cancer Metastasis RNA Binding Proteins RNA Computational Biology EMT TGF-beta Exonuclease Digestion 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. 2015-07-27 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957 http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Bioinformatics
Biology
Biomedical Research
Biostatistics
Cancer Metastasis
RNA Binding Proteins
RNA
Computational Biology
EMT
TGF-beta
Exonuclease Digestion
spellingShingle Bioinformatics
Biology
Biomedical Research
Biostatistics
Cancer Metastasis
RNA Binding Proteins
RNA
Computational Biology
EMT
TGF-beta
Exonuclease Digestion
Brown, Andrew S.
Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition
author Brown, Andrew S.
author_facet Brown, Andrew S.
author_sort Brown, Andrew S.
title Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition
title_short Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition
title_full Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition
title_fullStr Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition
title_full_unstemmed Identification of a phospho-hnRNP E1 Nucleic Acid Consensus Sequence Mediating Epithelial to Mesenchymal Transition
title_sort identification of a phospho-hnrnp e1 nucleic acid consensus sequence mediating epithelial to mesenchymal transition
publisher Kent State University / OhioLINK
publishDate 2015
url http://rave.ohiolink.edu/etdc/view?acc_num=kent1437943957
work_keys_str_mv AT brownandrews identificationofaphosphohnrnpe1nucleicacidconsensussequencemediatingepithelialtomesenchymaltransition
_version_ 1719438615145086976

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