Post-Transcriptional Regulation of The Eukaryotic Transcriptome by The Covalent RNA Modification N6-Methyladenosine / Stephen James Anderson.

Format:

Book

Thesis/Dissertation

Author/Creator:

Anderson, Stephen James, author.

Contributor:

Gregory, Brian D., degree supervisor.

University of Pennsylvania. Department of Biology, degree granting institution.

Language:

English

Subjects (All):

Molecular biology.

Bioinformatics.

Physiology.

Genetics.

Biology--Penn dissertations.

Penn dissertations--Biology.

Local Subjects:

Molecular biology.

Bioinformatics.

Physiology.

Genetics.

Biology--Penn dissertations.

Penn dissertations--Biology.

Genre:

Academic theses.

Physical Description:

1 online resource (263 pages)

Contained In:

Dissertations Abstracts International 81-02B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2019.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

Once a messenger RNA molecule is transcribed, a myriad of RNA fate decisions must be made. How these fate decisions are made is often unclear, and elucidating factors determining these fate outcomes is an essential task in order to fully understand gene regulation. One poorly- understood but undoubtedly important factor in post-transcriptional gene regulation is the covalent modification of ribonucleotides. Much like DNA can have chemical groups added to a nucleotide within its primary sequence, RNA can be modified in a similar manner. These covalent modifications of RNA are a ubiquitous feature found within the RNA of all organisms. Dozens of these modifications have been described to date, yet the function or importance of most of these modifications remains unclear. One crucial RNA modification is N6-methyladenosine (m6A), as it is the most abundant known non-cap modification within the eukaryotic transcriptome. In this work, we characterize the role of m6A in the Arabidopsis transcriptome using various sequencing methods that demonstrate that m6A is an abundant mark that is largely maintained across differing Arabidopsis tissues and developmental stages. This prevalent mark promotes transcript stability in mNRAs involved in many important and diverse biological processes, such as salt stress. The absence of this mark results in endonucleolytic cleavage and degradation of the transcript in a highly specific and local manner. We further demonstrate that this modification modulates secondary structure throughout the transcriptome, and that m6A is associated with changes in RNA-binding protein association. Lastly, we turn our view to how an association between m6A and the m6A-specific binding protein YTHDC1 influences the development and transcriptome-wide splicing and polyadenylation pattern in the mouse germline. We demonstrate that in the absence of YTHDC1, widespread developmental, splicing, and polyadenylation defects occur, resulting in non-functional gametes. In total, this work greatly expands our knowledge and understanding of the biological importance and mechanisms of m6A-mediated post-transcriptional regulation.

Notes:

Source: Dissertations Abstracts International, Volume: 81-02, Section: B.

Includes supplementary digital materials.

Advisors: Gregory, Brian D.; Committee members: R. Poethig; Doris Wagner; Junhyong Kim; Jeremy Wilusz.

Department: Biology.

Ph.D. University of Pennsylvania 2019.

Local Notes:

School code: 0175

ISBN:

9781085589406

Access Restriction:

Restricted for use by site license.

This item is not available from ProQuest Dissertations & Theses.

This item must not be sold to any third party vendors.