Elucidating the Noncatalytic and Catalytic Roles of Ribosome Biogenesis Factors in rRNA Processing and Nucleolar Organization Heidi Elashal

Format:

Book

Thesis/Dissertation

Author/Creator:

Elashal, Heidi, author.

Contributor:

University of Pennsylvania. Biochemistry and Molecular Biophysics., degree granting institution.

Language:

English

Subjects (All):

0307.

0379.

0487.

Local Subjects:

0307.

0379.

0487.

Physical Description:

1 electronic resource (184 pages)

Contained In:

Dissertations Abstracts International 87-07B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2025

Language Note:

English

Summary:

Ribosome biogenesis is a tightly coordinated process which involves several protein assembly factors and the processing and chemical modification of ribosomal RNAs (rRNAs) for the production of ribosomal subunits within the nucleolus. Disruption of this process has been linked to numerous human diseases and can have catastrophic consequences on nucleolar organization and cell proliferation. However, the detailed mechanisms by which protein assembly factors influence the cell's processes and architecture are poorly understood. We sought to understand the structure-function relationship of two distinct enzymes, EMG1 and DIMT1, which have structural noncatalytic roles in supporting 40S small subunit assembly and catalytic roles in methylating 18S rRNA. In the case of EMG1, residue Arg84 in the protein's positively charged RNA binding groove is identified in regulating rRNA processing and cell proliferation. DIMT1's RNA binding cleft (consisting of Arg162, Arg174, Arg228, Lys253, and Arg256) functions similarly, but in addition, uniquely controls the protein's canonical nucleolar localization. The nucleolus is a multilayered structure which is important for rRNA processing and ribosome assembly. Notably, we found that this nucleolar compartmentalization is preserved by the proper cleavage of the 5' external transcribed spacer (5'ETS), and depleting protein factors involved in this processing step results in the formation of a single large DAPI-negative nuclear structure and the mislocalization of newly synthesized RNA. Altogether, these findings advance our knowledge of how protein assembly factors contribute to ribosome formation and nucleolar architecture and can be leveraged to target the many ribosomal proteins linked to disease

Notes:

Advisors: Liu, Kathy Fange Committee members: Van Duyne, Gregory; Tian, Bin; Conn, Crystal

Source: Dissertations Abstracts International, Volume: 87-07, Section: B.

Ph.D. University of Pennsylvania 2025

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798276001456

Access Restriction:

Restricted for use by site license