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Regulation of ELAVL RNA binding proteins promotes neuronal diversity in the neocortex

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Title
Regulation of ELAVL RNA binding proteins promotes neuronal diversity in the neocortex
Name (type = personal)
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Popovitchenko
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Tatiana
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Tatiana Popovitchenko
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author
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D'Arcangelo
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Gabriella
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Gabriella D'Arcangelo
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Advisory Committee
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chair
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Rongo
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Christopher
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Christopher Rongo
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Advisory Committee
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internal member
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Rasin
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Mladen-Roko
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Mladen-Roko Rasin
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Advisory Committee
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internal member
Name (type = personal)
NamePart (type = family)
DiCicco-Bloom
NamePart (type = given)
Emanuel
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Emanuel DiCicco-Bloom
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Advisory Committee
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internal member
Name (type = personal)
NamePart (type = family)
Kiledjian
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Megerditch
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Megerditch Kiledjian
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Advisory Committee
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outside member
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Rutgers University
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degree grantor
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School of Graduate Studies
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school
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Text
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theses
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2021
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2021-01
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2020
Language
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English
Abstract (type = abstract)
The diversity of neurons in the neocortex endows that structure with its wide range of abilities. It is likely the interplay of proteins on extracellular, transcriptional, and post-transcriptional levels that determines cell type diversity in the neocortex. Of these, post-transcriptional processes are especially important for the time sensitive steps of neuronal development. This thesis explores the mechanisms by which two RNA Binding Proteins (RBPs), in the Embryonic Lethal and Abnormal Vision Like (Elavl) protein family, promote diversity of neurons during neocorticogenesis.

ELAVL1, also known as Hu antigen R (HuR), is a ubiquitously expressed RBP. We found that HuR binds over 7,000 targets during neocortical development. Specifically, it discriminates between Foxp1 and Foxp2 mRNA targets to define the respective identities of those two subpopulations of neocortical pyramidal neurons. Additionally, I discovered that phosphorylation sites throughout mouse HuR/ELAVL1 likely regulate target discrimination.

In addition to phosphorylation sites on RBPs, alternative 3’ and 5’ untranslated regions (UTRs) can allow for target discrimination by RBPs. Within the embryonic mouse neocortex, we found a wide-spread pattern of repression and derepression of mRNA translation. I found that specific isoforms of the Hu antigen D (HuD/ELAVL4) RBP are repressed by the CUG-binding protein 1/CUG-BP-Elav like family 1 (CUGBP1/CELF1) RBP up to embryonic day 16. CUGBP1/CELF1 is able to discriminate amongst HuD/ELAVL4 isoforms through its alternative 5’UTRs.

In sum, the ability to differentiate among RNA transcripts directly leads to an RBP’s role in determining cellular diversity through subpopulation identity. Regulation of RBPs, at the post-translational level through phosphorylation and at the post-transcriptional level through alternative 5’utrs, promotes neocortical cell type diversity.
Subject (authority = local)
Topic
Neuroscience
Subject (authority = RUETD)
Topic
Neuroscience
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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ETD_11304
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application/pdf
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text/xml
Extent
1 online resource (xiv, 209 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Genre (authority = ExL-Esploro)
ETD doctoral
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Title
School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/t3-rcw0-xs37
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Popovitchenko
GivenName
Tatiana
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2020-11-05 14:11:31
AssociatedEntity
Name
Tatiana Popovitchenko
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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License
Name
Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Copyright protected
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Status
Open
Reason
Permission or license
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2020-11-09T23:43:37
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2020-11-09T23:43:37
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