Multilayered regulation of translation: roles of rRNA modifications, alternative initiation factors, and RNA-binding proteins
Chen, Xin
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https://hdl.handle.net/2142/132800
Description
Title
Multilayered regulation of translation: roles of rRNA modifications, alternative initiation factors, and RNA-binding proteins
Author(s)
Chen, Xin
Issue Date
2025-12-04
Director of Research (if dissertation) or Advisor (if thesis)
Jin, Hong
Doctoral Committee Chair(s)
Jin, Hong
Committee Member(s)
Fratti, Rutilio A
Wu, Nicholas
Zhang, Yan
Department of Study
School of Molecular & Cell Bio
Discipline
Biophysics & Quant Biology
Degree Granting Institution
University of Illinois Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
translation
ribosome
Language
eng
Abstract
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.
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