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Novel Protein Regulators of Human Ribosome Biogenesis.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Novel Protein Regulators of Human Ribosome Biogenesis./
作者:	McCool, Mason Alexander.
面頁冊數:	1 online resource (274 pages)
附註:	Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
Contained By:	Dissertations Abstracts International85-01B.
標題:	Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30312679click for full text (PQDT)
ISBN:	9798379782252

Novel Protein Regulators of Human Ribosome Biogenesis.
McCool, Mason Alexander.

Novel Protein Regulators of Human Ribosome Biogenesis. - 1 online resource (274 pages)

Source: Dissertations Abstracts International, Volume: 85-01, Section: B.

Thesis (Ph.D.)--Yale University, 2023.

Includes bibliographical references

Ribosome biogenesis is the essential process that all living organisms need to produce the protein synthesizing machinery within cells. It has become apparent in recent years that ribosome biogenesis in higher eukaryotes, like humans, is increasingly complex. When this process becomes dysregulated it can lead to diseases, such as cancer when upregulated and ribosomopathies when inhibited, emphasizing the importance of learning more about the process of making ribosomes. To identify novel regulators of human ribosome biogenesis, the Baserga laboratory previously developed and performed a genome-wide RNAi screen. Here, I build upon those findings to interrogate the function of a handful of these novel human ribosome biogenesis regulators. After discovery that one of the novel regulators, CRK, likely represents an siRNA off-target effect, I helped validate the original screen results by performing a new 5-EU incorporation assay testing for more functional roles in nucleolar ribosomal RNA biogenesis. Next, I examined the molecular functions of high-confidence individual hits in the ribosome biogenesis pathway. I discovered that NOL7 is the likely ortholog of yeast Bud21 and is required for early pre-ribosomal RNA stability. I showed that large subunit biogenesis factors, RSL24D1 and the PeBoW (PES1-BOP1-WDR12) complex, interact with and regulate RNA polymerase I levels. Finally, I studied the cytidine deaminase, APOBEC3A's, function in large ribosomal subunit biogenesis. In doing so, I reveal for the first time the possibility that the pre-ribosomal RNA can be edited by this enzyme during its maturation. These results underscore the nuances of human ribosome biogenesis regulation and push forward our understanding of this essential process with implications in treatment of disease, primarily cancer.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798379782252Subjects--Topical Terms:

518028
Biochemistry.
Subjects--Index Terms:

RibosomeIndex Terms--Genre/Form:

542853
Electronic books.

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