The Role of Alternative Polyadenylation in Genome Function and Health Implications

Shane A. Carrion

doi:10.7273/000006543

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The Role of Alternative Polyadenylation in Genome Function and Health Implications

Dissertation

Open access

The Role of Alternative Polyadenylation in Genome Function and Health Implications

Shane A. Carrion

Washington State University

Doctor of Philosophy (PhD), Washington State University

05/2024

DOI:

https://doi.org/10.7273/000006543

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Supplemental Table 1 Final Collection of Imprinted Genes117.01 kBDownload View

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Supplemental Table 2 Final Sex Differentiation Genes21.05 kBDownload View

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Abstract

Alternative Polyadenylation

Comparative Genomics

Health and disease relevance

Parent of Origin

RNA variants

Evolution & development

Transcript diversity is a key biological advantage in complex lifeforms, allowing an organism to manufacture a wide range of transcript and gene products from a limited selection of genes. Of the three main mechanisms of transcript diversity (alternative splicing, alternative transcription start, and alternative polyadenylation), alternative polyadenylation or APA, has the highest impact on proteins alongside alternative start sites. APA is prevalent in eukaryotes, evolutionarily conserved, and more than 50% of human genes contain 3 or more APA sites. Imprinted genes, which display monoallelic expression on a parent-of-origin specific basis due to epigenetic modifications, remain a unique and still underexplored gene set. This offered the opportunity to explore what unique traits imprinted genes shared compared to a set in the functionally similar sex differentiation set and investigate their use of APA sites and involvement in pathways from a cattle gene set whose APA patterns had been assigned. Despite the increase in study of APA over the past two decades, categorical and pathway APA patterning (gene and pathway specific) remained relatively unexplored. We demonstrated a method of categorizing APA site use using biological pathways, such as gene ontology, on pathways with a specific focus, in this instance hormones. Hormones have strong regulatory effects throughout the body, meaning misregulation of these pathways can quickly lead to disease states. Hormone clusters formed using APA profiles (assigned by APA patterning), combined with other factors, displayed coherent function, with each cluster displaying a unique APA profile. APA profiling also allows for identification of distinct profile differences between related groups and links with pathways outside of the explored class.

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Details

Title: The Role of Alternative Polyadenylation in Genome Function and Health Implications
Creators: Shane A. Carrion
Contributors: Zhihua Jiang (Chair)
Min Du (Committee Member)
Erica Crespi (Committee Member)
Lisette Maddison (Committee Member)
Awarding Institution: Washington State University
Academic Unit: Animal Sciences, Department of
Theses and Dissertations: Doctor of Philosophy (PhD), Washington State University
Publisher: Washington State University
Number of pages: 144
Identifiers: 99901121437501842
Language: English
Resource Type: Dissertation