Killing the Messenger: Exploring Novel Triggers for Messenger RNA Decay in Eukaryotes / Lee E Vandivier.

Format:

Book

Thesis/Dissertation

Author/Creator:

Vandivier, Lee E., author.

Contributor:

Gregory, Brian D., degree supervisor.

Wagner, Doris, degree committee member.

Poethig, R. Scott, degree committee member.

Mourelatos, Zissimos, degree committee member.

Meyers, Blake C., degree committee member.

University of Pennsylvania. Cell and Molecular Biology, degree granting institution.

Language:

English

Subjects (All):

Biology.

Bioinformatics.

Genetics.

Cell and Molecular Biology--Penn dissertations.

Penn dissertations--Cell and Molecular Biology.

Local Subjects:

Biology.

Bioinformatics.

Genetics.

Cell and Molecular Biology--Penn dissertations.

Penn dissertations--Cell and Molecular Biology.

Genre:

Academic theses.

Physical Description:

1 online resource (228 pages)

Contained In:

Dissertation Abstracts International 79-01B(E).

Place of Publication:

[Philadelphia, Pennsylvania]: University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2017.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

The lifecycle of messenger RNAs is regulated by multiple layers beyond their primary sequence. In addition to carrying the information for protein synthesis, mRNAs are decorated with RNA binding proteins, marked with covalent chemical modifications, and fold into intricate secondary structures. However, the full set of information encoded by these "epitranscriptomic" layers is only partially understood, and is often only characterized for select transcripts. Thus, it is crucial to develop and apply transcriptome-wide analytical tools to probe the location and functional relevance of epitranscriptome features. In this dissertation, I focus on applying such methods toward better understanding determinants of mRNA stability, through using 1) High Throughput Annotation of Modified Nucleotides, 2) nuclease-mediated probing of RNA secondary structure, and 3) detection of partial mRNA degradation from RNA sequencing. I observe that chemical modifications tend to mark uncapped and small RNA fragments derived from mRNAs in plants and humans, suggesting a link between modifications and mRNA stability. I then show this link is direct through showing differential stability at Arabidopsis transcripts that change modification status during long-term salt stress. By probing secondary structure, I show a link between structure, smRNA production, and co-translational RNA decay. Finally, I develop a new in silico method to detect partial RNA degradation in mouse oocytes, and identify sequence elements that appear to block complete exonucleolytic transcript cleavage during meiosis. I then identify putative RNA binding proteins that might mediate this partial decay. In summary, I apply transcriptome-wide sequencing-based methods to survey the effects of covalent modifications, secondary structure, and RNA binding proteins on mRNA stability.

Notes:

Source: Dissertation Abstracts International, Volume: 79-01(E), Section: B.

Advisors: Brian D. Gregory; Committee members: Blake C. Meyers; Zissimos Mourelatos; R. Scott Poethig; Doris Wagner.

Department: Cell and Molecular Biology.

Ph.D. University of Pennsylvania 2017.

Local Notes:

School code: 0175

ISBN:

9780355183160

Access Restriction:

Restricted for use by site license.