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Dual nuclear roles of an essential scavenger decapping enzyme
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Dual nuclear roles of an essential scavenger decapping enzyme
Identifier
ETD_2748
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056772
Language
LanguageTerm
(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Biochemistry
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
RNA--Research
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Mice--Development
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Mice--Cytology
Abstract
(type = abstract)
The broad findings of the current work focus on mammalian DcpS and provide an analysis of its role in pre-mRNA splicing, transcription, and its requirement in mouse development. Mutagenesis and heterokaryon assays reveal an N-terminal nuclear localization sequence and a central nuclear export sequence that account for its nucleocytoplasmic dynamics. Cell-based reporter assays reveal two novel DcpS nuclear roles that explain its prevalent nuclear presence. A cell-based mRNA assay, which detects reporter splicing patterns, indicates DcpS knockdown leads to pre-mRNA processing deficiency in the first intron. DcpS or Cbp20 overexpression partially and completely corrects this defect, respectively. Catalytically inactive DcpS displaces the Cbp20-cap interaction by competition in a reconstituted system. These results suggest DcpS is a positive regulator of pre-mRNA splicing and is in line with the idea that DcpS knockdown predictably upregulates intracellular cap structure levels. Another cell-based translation assay, which detects reporter enzyme activity, shows DcpS chemical repression or knockdown stimulates cap-dependent translation and reduces 4EBP1 protein level. The unexpected opposite effect on translation suggests DcpS catalysis does not directly regulate protein synthesis as previously thought. DcpS chemical repression by a competitive inhibitor leads to 4EBP1 and 4EBP2 transcriptional reductions that correlate with their steady state mRNA levels. These results point toward an additional DcpS nuclear role in transcription of specific targets. On a final note, the failure to generate DcpS homozygous progeny as early as 6 days post coitum (dpc) indicates this gene is essential for mouse embryogenesis. DcpS heterozygous intercross yields approximately two heterozygotes for each wildtype during 9.5 dpc and postnatal period. DcpS heterozygotes are normal with respect to fertility. Western blots show DcpS is ubiquitously expressed in an adult tissue panel comprised of brain, liver, kidney, and heart. The present study identifies at least two nuclear roles of DcpS in pre-mRNA first intron splicing and in transcription, and its essential role in mouse development.
PhysicalDescription
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electronic resource
Extent
ix, 110 p. : ill.
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application/pdf
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text/xml
Note
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Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Vincent Shen
Name
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(type = family)
Shen
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Vincent
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author
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VINCENT SHEN
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NamePart
(type = family)
Kiledjian
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Mike
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chair
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Advisory Committee
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Mike Kiledjian
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NamePart
(type = family)
Gunderson
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(type = given)
Sam
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internal member
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Advisory Committee
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Sam Gunderson
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(type = personal)
NamePart
(type = family)
Kinzy
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(type = given)
Terri
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internal member
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Advisory Committee
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Terri Kinzy
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(ID = NAME-5);
(type = personal)
NamePart
(type = family)
Copeland
NamePart
(type = given)
Paul
Role
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outside member
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Advisory Committee
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Paul Copeland
Name
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NamePart
Rutgers University
Role
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degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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(authority = RULIB)
school
OriginInfo
DateCreated
(qualifier = exact)
2010
DateOther
(qualifier = exact);
(type = degree)
2010-10
Place
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(type = code)
xx
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Identifier
(type = doi)
doi:10.7282/T3DF6QZT
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
SHEN
GivenName
VINCENT
Role
Copyright Holder
RightsEvent
(ID = RE-1);
(AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-06-04 13:20:30
AssociatedEntity
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(AUTHORITY = rulib)
Role
Copyright holder
Name
VINCENT SHEN
Affiliation
Rutgers University. Graduate School - New Brunswick
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License
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Author Agreement License
Detail
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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Technical
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ETD
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application/pdf
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application/x-tar
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1587200
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