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Bioinformatic analysis of polyadenylation site activity in vertebrates

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Bioinformatic analysis of polyadenylation site activity in vertebrates
Identifier
ETD_2805
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056368
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-protein interactions
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Bioinformatics
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Logistic regression analysis
Abstract (type = abstract)
Most eukaryotic protein coding precursor messenger RNAs (pre-mRNAs) undergo polyadenylation after transcription. Polyadenylation is a two-step enzymatic reaction, in which the emerging pre-mRNA is cleaved from the transcription complex, and then followed by the polymerization of adenosine nucleotides starting from the cleaved 3‟ end to form the poly(A) tail. Biologically, poly(A) tail increases mRNA stability, protein translatability, and mRNA nuclear export. Surprisingly, large numbers of protein factors were found to be involved in this apparently simple cleavage and polymerization steps, suggesting that polyadenylation is under complex regulation. Hence in this study, I am interested to investigate the regulatory elements of eukaryotic polyadenylation. The proposed close species comparison approach revealed an asymmetric selection pressure around the polyadenylation cleavage site (PAS). The region from the PAS to approximately 200 nucleotides (nts) upstream was found to be under a much higher conservation than the downstream region and other part of the 3‟UTR. Furthermore, over 2,000 long (>30 nts) conserved fragments at or close to upstream of the PAS were identified through remote species comparison. A substantial portion of them are longer than 100 nts, which is much longer than any known RNA protein recognition sites. A PAS classifier was built using logistic regression in order to study the characteristics of PAS. Not only it does improve the computational recognition of mammalian PAS than existing methods, it is also helpful in identifying a small number of genes that lack of typical PAS characteristics such as the poly(A) signal and/or the U/GU rich region. These findings provide useful experimental candidates for the study of the still unclear polyadenylation compensatory and/or regulatory elements. At present, no sequence consensus has been identified for the downstream U/GU enriched region yet. Thus, I have designed a novel rule-based nucleotide sequence motif finding algorithm, called iTriplet, to target long and degenerative motifs with special attention to the PAS downstream sequence. iTriplet has been demonstrated to handle motifs longer than 20 nts, which is still a challenge to existing methods. The utility of iTriplet has been confirmed by showing it accurately predicts PAS downstream elements using a dual Luciferase reporter assay.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
xiv, 200 p. : ill.
InternetMediaType
application/pdf
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text/xml
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Eric Sau-Chum Ho
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Ho
NamePart (type = given)
Eric Sau-Chum
NamePart (type = date)
1963-
Role
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author
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Eric Ho
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
GUNDERSON
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SAMUEL I
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chair
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Advisory Committee
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SAMUEL I GUNDERSON
Name (ID = NAME-3); (type = personal)
NamePart (type = family)
Hey
NamePart (type = given)
Jody
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internal member
Affiliation
Advisory Committee
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Jody Hey
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Cai
NamePart (type = given)
Li
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Li Cai
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Tian
NamePart (type = given)
Bin
Role
RoleTerm (authority = RULIB)
outside member
Affiliation
Advisory Committee
DisplayForm
Bin Tian
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010
Place
PlaceTerm (type = code)
xx
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3611031
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (AUTHORITY = GS); (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
Ho
GivenName
Eric
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-08-09 13:20:17
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Eric Ho
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
Type
License
Name
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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ETD
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application/pdf
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application/x-tar
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Checksum (METHOD = SHA1)
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