{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/132515"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/132515","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Mechanisms of transcription and translation dysfunction in disease: a novel FMRP-translation axis in Alzheimer’s and expansion of Pol III transcription in cancer","abstract":"Gene regulation operates across multiple layers, from chromatin state to RNA processing and translation. Crucially, a gene encodes an RNA molecule before it ever becomes a protein, and RNAs themselves are diverse in form and function. Dysregulation of RNA pathways is implicated in many diseases, like cancer, neurological and immunological disorders, and cardiovascular disease. This dissertation examines RNA biology from complementary angles spanning mechanism, genomics, and methods. Chapter 1 provides a brief overview of RNA biology, emphasizing that RNAs are not merely intermediates in carrying DNA information but active regulators. It surveys regulatory mechanisms at the DNA, transcriptional, and translational levels to frame the chapters that follow. Chapter 2 investigates translational control in an in vitro Alzheimer’s disease model, focusing on the RNA-binding protein Fragile X Messenger Ribonucleoprotein (FMRP). I describe a previously unrecognized mechanism by which FMRP modulates translation under amyloid-β induces toxicity, proposing FMRP as one of several factors that could influence and contribute with AD progression. Chapter 3 turns to large-scale analysis and introduces, the first multi-tissue and tumor atlas of RNA polymerase III (Pol III) transcribed genes accessibility. By integrating more than 500 ATAC-seq datasets, I address the challenges in assaying short, highly similar Pol III transcripts. The atlas resolves housekeeping, tissue-specific, and cancer-emergent Pol III gene sets and proposes regulatory features that may explain the observed context specificity. Motivated by the analytical hurdles encountered in these studies, Chapter 4 presents dominatR, an R package for visualizing feature dominance across contexts. The tool interoperates with the Bioconductor ecosystem and is released as a publicly available resource. Chapter 5 synthesizes the main findings, outlines limitations of the experimental and computational approaches, and proposes concrete directions for future work. Together, these studies expand our understanding of RNA-centered regulation across molecular layers and disease contexts, combining mechanistic insight, atlas-scale genomics, and open-source tools.","abstract_html":"Gene regulation operates across multiple layers, from chromatin state to RNA processing and translation. Crucially, a gene encodes an RNA molecule before it ever becomes a protein, and RNAs themselves are diverse in form and function. Dysregulation of RNA pathways is implicated in many diseases, like cancer, neurological and immunological disorders, and cardiovascular disease. This dissertation examines RNA biology from complementary angles spanning mechanism, genomics, and methods. Chapter 1 provides a brief overview of RNA biology, emphasizing that RNAs are not merely intermediates in carrying DNA information but active regulators. It surveys regulatory mechanisms at the DNA, transcriptional, and translational levels to frame the chapters that follow. Chapter 2 investigates translational control in an in vitro Alzheimer’s disease model, focusing on the RNA-binding protein Fragile X Messenger Ribonucleoprotein (FMRP). I describe a previously unrecognized mechanism by which FMRP modulates translation under amyloid-β induces toxicity, proposing FMRP as one of several factors that could influence and contribute with AD progression. Chapter 3 turns to large-scale analysis and introduces, the first multi-tissue and tumor atlas of RNA polymerase III (Pol III) transcribed genes accessibility. By integrating more than 500 ATAC-seq datasets, I address the challenges in assaying short, highly similar Pol III transcripts. The atlas resolves housekeeping, tissue-specific, and cancer-emergent Pol III gene sets and proposes regulatory features that may explain the observed context specificity. Motivated by the analytical hurdles encountered in these studies, Chapter 4 presents dominatR, an R package for visualizing feature dominance across contexts. The tool interoperates with the Bioconductor ecosystem and is released as a publicly available resource. Chapter 5 synthesizes the main findings, outlines limitations of the experimental and computational approaches, and proposes concrete directions for future work. Together, these studies expand our understanding of RNA-centered regulation across molecular layers and disease contexts, combining mechanistic insight, atlas-scale genomics, and open-source tools.","abstract_has_math":false,"creators":["Lizarazo Chaparro, Simon"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular & Integrative Physi","degree_department":null,"school":null,"contributors":["Tsai, Nien Pei","Van Bortle, Kevin","Chung, Hee Jung","Zhao, Dave Sihao"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-12","date_published":"2025-12","updated_at":"2026-07-22T22:25:07Z","subjects":["RNA Polymerase III","Cancer","Functional Genomics","Alzheimer's Disease","FMRP","Bioinformatics","Neurobiology"],"languages":["en"],"rights":["Copyright 2025 Simon Lizarazo Chaparro"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/132515","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Tsai, Nien Pei","Van Bortle, Kevin","Chung, Hee Jung","Zhao, Dave Sihao"]},{"key":"dc:creator","label":"Author","values":["Lizarazo Chaparro, Simon"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-12","2025-12-01"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular & Integrative Physi"]},{"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":["RNA Polymerase III","Cancer","Functional Genomics","Alzheimer's Disease","FMRP","Bioinformatics","Neurobiology"]}]},{"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 Simon Lizarazo Chaparro"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/132515"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Gene regulation operates across multiple layers, from chromatin state to RNA processing and translation. Crucially, a gene encodes an RNA molecule before it ever becomes a protein, and RNAs themselves are diverse in form and function. Dysregulation of RNA pathways is implicated in many diseases, like cancer, neurological and immunological disorders, and cardiovascular disease. This dissertation examines RNA biology from complementary angles spanning mechanism, genomics, and methods. Chapter 1 provides a brief overview of RNA biology, emphasizing that RNAs are not merely intermediates in carrying DNA information but active regulators. It surveys regulatory mechanisms at the DNA, transcriptional, and translational levels to frame the chapters that follow. Chapter 2 investigates translational control in an in vitro Alzheimer’s disease model, focusing on the RNA-binding protein Fragile X Messenger Ribonucleoprotein (FMRP). I describe a previously unrecognized mechanism by which FMRP modulates translation under amyloid-β induces toxicity, proposing FMRP as one of several factors that could influence and contribute with AD progression. Chapter 3 turns to large-scale analysis and introduces, the first multi-tissue and tumor atlas of RNA polymerase III (Pol III) transcribed genes accessibility. By integrating more than 500 ATAC-seq datasets, I address the challenges in assaying short, highly similar Pol III transcripts. The atlas resolves housekeeping, tissue-specific, and cancer-emergent Pol III gene sets and proposes regulatory features that may explain the observed context specificity. Motivated by the analytical hurdles encountered in these studies, Chapter 4 presents dominatR, an R package for visualizing feature dominance across contexts. The tool interoperates with the Bioconductor ecosystem and is released as a publicly available resource. Chapter 5 synthesizes the main findings, outlines limitations of the experimental and computational approaches, and proposes concrete directions for future work. Together, these studies expand our understanding of RNA-centered regulation across molecular layers and disease contexts, combining mechanistic insight, atlas-scale genomics, and open-source tools.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2026-02-19 without embargo terms","The student, Simon Lizarazo Chaparro, accepted the attached license on 2025-11-20 at 10:14.","The student, Simon Lizarazo Chaparro, submitted this Dissertation for approval on 2025-11-20 at 10:28.","This Dissertation was approved for publication on 2025-12-01 at 07:44.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22908 on 2026-02-19 at 18:25:09"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Mechanisms of transcription and translation dysfunction in disease: a novel FMRP-translation axis in Alzheimer’s and expansion of Pol III transcription in cancer"]}]}],"canonical_facts":{"dc:contributor":["Tsai, Nien Pei","Van Bortle, Kevin","Chung, Hee Jung","Zhao, Dave Sihao"],"dc:creator":["Lizarazo Chaparro, Simon"],"dc:date":["2025-12","2025-12-01"],"dc:description":["Gene regulation operates across multiple layers, from chromatin state to RNA processing and translation. Crucially, a gene encodes an RNA molecule before it ever becomes a protein, and RNAs themselves are diverse in form and function. Dysregulation of RNA pathways is implicated in many diseases, like cancer, neurological and immunological disorders, and cardiovascular disease. This dissertation examines RNA biology from complementary angles spanning mechanism, genomics, and methods. Chapter 1 provides a brief overview of RNA biology, emphasizing that RNAs are not merely intermediates in carrying DNA information but active regulators. It surveys regulatory mechanisms at the DNA, transcriptional, and translational levels to frame the chapters that follow. Chapter 2 investigates translational control in an in vitro Alzheimer’s disease model, focusing on the RNA-binding protein Fragile X Messenger Ribonucleoprotein (FMRP). I describe a previously unrecognized mechanism by which FMRP modulates translation under amyloid-β induces toxicity, proposing FMRP as one of several factors that could influence and contribute with AD progression. Chapter 3 turns to large-scale analysis and introduces, the first multi-tissue and tumor atlas of RNA polymerase III (Pol III) transcribed genes accessibility. By integrating more than 500 ATAC-seq datasets, I address the challenges in assaying short, highly similar Pol III transcripts. The atlas resolves housekeeping, tissue-specific, and cancer-emergent Pol III gene sets and proposes regulatory features that may explain the observed context specificity. Motivated by the analytical hurdles encountered in these studies, Chapter 4 presents dominatR, an R package for visualizing feature dominance across contexts. The tool interoperates with the Bioconductor ecosystem and is released as a publicly available resource. Chapter 5 synthesizes the main findings, outlines limitations of the experimental and computational approaches, and proposes concrete directions for future work. Together, these studies expand our understanding of RNA-centered regulation across molecular layers and disease contexts, combining mechanistic insight, atlas-scale genomics, and open-source tools.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2026-02-19 without embargo terms","The student, Simon Lizarazo Chaparro, accepted the attached license on 2025-11-20 at 10:14.","The student, Simon Lizarazo Chaparro, submitted this Dissertation for approval on 2025-11-20 at 10:28.","This Dissertation was approved for publication on 2025-12-01 at 07:44.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22908 on 2026-02-19 at 18:25:09"],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/132515"],"dc:language":["en"],"dc:rights":["Copyright 2025 Simon Lizarazo Chaparro"],"dc:subject":["RNA Polymerase III","Cancer","Functional Genomics","Alzheimer's Disease","FMRP","Bioinformatics","Neurobiology"],"dc:title":["Mechanisms of transcription and translation dysfunction in disease: a novel FMRP-translation axis in Alzheimer’s and expansion of Pol III transcription in cancer"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Molecular & Integrative Physi"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:07Z"}