Multilayered regulation of translation: roles of rRNA modifications, alternative initiation factors, and RNA-binding proteins

Translation is a central process in gene expression, where the ribosome decodes mRNA to synthesize proteins. This dissertation explores distinct regulatory layers that influence translation initiation and ribosome function, focusing on alternative initiation factors, ribosomal RNA modifications, and RNA-binding proteins. First, structural and genomic analyses of the alternative initiation factor eIF2A reveal its contributions to non-canonical initiation events. Loss of eIF2A reduces ribosome occupancy at the start codon region of specific genes, suggesting a role in stabilizing pre-initiation complexes or facilitating start codon recognition under specialized conditions. Second, we investigate the functional significance of conserved pseudouridines in Helix 69 of the ribosome. Using genomic and biochemical approaches, we show that the absence of these modifications alters ribosome dynamics, increases frameshifting, impairs internal ribosome entry site mediated translation, and compromises translational fidelity. Finally, the intrinsically disordered RNA-binding protein Sbp1 is examined for its role in translational regulation and mRNA storage. Our findings indicate that Sbp1 modulates translation efficiency and participates in mRNA sequestration into ribonucleoprotein granules, influencing cellular responses to environmental stress. Together, these studies provide how translation initiation and elongation are fine-tuned through diverse molecular mechanisms, advancing our understanding of translational control in eukaryotic cells.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics & Quant Biology

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Chen, Xin

Contributors dc:contributor

• Jin, Hong
• Fratti, Rutilio A
• Wu, Nicholas
• Zhang, Yan

• translation
• ribosome

Statement dc:rights

• Copyright © 2025 by Xin Chen. All rights reserved.

Language dc:language

en

Handle dc:identifier

https://hdl.handle.net/2142/132800

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/132800