{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/132800"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/132800","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Multilayered regulation of translation: roles of rRNA modifications, alternative initiation factors, and RNA-binding proteins","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Chen, Xin"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics & Quant Biology","degree_department":null,"school":null,"contributors":["Jin, Hong","Fratti, Rutilio A","Wu, Nicholas","Zhang, Yan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-12","date_published":"2025-12","updated_at":"2026-07-22T22:25:07Z","subjects":["translation","ribosome"],"languages":["en"],"rights":["Copyright © 2025 by Xin Chen. All rights reserved."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/132800","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jin, Hong","Fratti, Rutilio A","Wu, Nicholas","Zhang, Yan"]},{"key":"dc:creator","label":"Author","values":["Chen, Xin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-12","2025-12-04"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics & Quant Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["translation","ribosome"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright © 2025 by Xin Chen. All rights reserved."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/132800"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-12-01","The student, Xin Chen, accepted the attached license on 2025-12-04 at 15:48.","The student, Xin Chen, submitted this Dissertation for approval on 2025-12-04 at 16:01.","This Dissertation was approved for publication on 2025-12-04 at 20:32.","DSpace SAF Submission Ingestion Package generated from Vireo submission #23065 on 2026-02-19 at 20:10:02"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Multilayered regulation of translation: roles of rRNA modifications, alternative initiation factors, and RNA-binding proteins"]}]}],"canonical_facts":{"dc:contributor":["Jin, Hong","Fratti, Rutilio A","Wu, Nicholas","Zhang, Yan"],"dc:creator":["Chen, Xin"],"dc:date":["2025-12","2025-12-04"],"dc:description":["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.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-12-01","The student, Xin Chen, accepted the attached license on 2025-12-04 at 15:48.","The student, Xin Chen, submitted this Dissertation for approval on 2025-12-04 at 16:01.","This Dissertation was approved for publication on 2025-12-04 at 20:32.","DSpace SAF Submission Ingestion Package generated from Vireo submission #23065 on 2026-02-19 at 20:10:02"],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/132800"],"dc:language":["en"],"dc:rights":["Copyright © 2025 by Xin Chen. All rights reserved."],"dc:subject":["translation","ribosome"],"dc:title":["Multilayered regulation of translation: roles of rRNA modifications, alternative initiation factors, and RNA-binding proteins"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Biophysics & Quant Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:07Z"}