Regulation of Oscillatory Gene Expression by Alternative Polyadenylation

Regulation of Oscillatory Gene Expression by Alternative Polyadenylation

Bibliographic Details
Main Author: Braunreiter, Kara M.
Language:English
Published: The Ohio State University / OhioLINK 2020
Subjects:
Molecular Biology
Genetics
Developmental Biology
alternative polyadenylation
somitogenesis
vertebrate segmentation
oscillatory gene expression
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1595517827933039
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu15955178279330392021-09-02T05:10:39Z Regulation of Oscillatory Gene Expression by Alternative Polyadenylation Braunreiter, Kara M. Molecular Biology Genetics Developmental Biology alternative polyadenylation somitogenesis vertebrate segmentation oscillatory gene expression Oscillatory genes control many processes during development and require very tight regulation to ensure proper expression. The oscillatory gene <i>Hes7</i> is required for proper vertebrate segmentation along the anterior-posterior axis and is highly conserved among vertebrate species. During vertebrate segmentation, a group of clock-linked genes oscillate with a species-specific period that matches the rate of the formation of transient structures called somites from the undifferentiated presomitic mesoderm (PSM). <i>Hes7</i> is one such clock-linked gene that is controlled through an auto-regulatory negative feedback loop, and mathematical models predict that the period of oscillation is influenced by the turnover rates of the mRNA and protein. Here I identify alternative <i>Hes7</i> transcript isoforms produced through alternative polyadenylation (APA) that have different lengths of 3’ untranslated region (UTR) for regulation. These isoforms may have different transcript half-lives and translational efficiency which could influence the period of the oscillations. Furthermore, I show that APA of <i>Hes7</i> is required for proper vertebrate segmentation by eliminating the production of longer isoforms in a mouse model. Mice only producing the shortest <i>Hes7</i> isoform still exhibit oscillatory expression of all clock linked genes, however they produce additional vertebrae and have abnormal sternal-rib attachments. In addition, I begin to address the mechanism of APA site selection by investigating a tRNA gene that lies within the 3’UTR of <i>Hes7</i> as well as a single nucleotide polymorphism (SNP) which affects APA site selection as well as tRNA processing. I predict that APA of oscillatory genes provides a mechanism to fine-tune the period of oscillations in a variety of developmental contexts. 2020 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1595517827933039 http://rave.ohiolink.edu/etdc/view?acc_num=osu1595517827933039 restricted--full text unavailable until 2025-08-02 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Molecular Biology
Genetics
Developmental Biology
alternative polyadenylation
somitogenesis
vertebrate segmentation
oscillatory gene expression
spellingShingle Molecular Biology
Genetics
Developmental Biology
alternative polyadenylation
somitogenesis
vertebrate segmentation
oscillatory gene expression
Braunreiter, Kara M.
Regulation of Oscillatory Gene Expression by Alternative Polyadenylation
author Braunreiter, Kara M.
author_facet Braunreiter, Kara M.
author_sort Braunreiter, Kara M.
title Regulation of Oscillatory Gene Expression by Alternative Polyadenylation
title_short Regulation of Oscillatory Gene Expression by Alternative Polyadenylation
title_full Regulation of Oscillatory Gene Expression by Alternative Polyadenylation
title_fullStr Regulation of Oscillatory Gene Expression by Alternative Polyadenylation
title_full_unstemmed Regulation of Oscillatory Gene Expression by Alternative Polyadenylation
title_sort regulation of oscillatory gene expression by alternative polyadenylation
publisher The Ohio State University / OhioLINK
publishDate 2020
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1595517827933039
work_keys_str_mv AT braunreiterkaram regulationofoscillatorygeneexpressionbyalternativepolyadenylation
_version_ 1719474143532941312

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