{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/115713"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/115713","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Regulated alternative splicing separates canonical and cell signaling functions of aminoacyl-tRNA synthetases","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","abstract_has_math":false,"creators":["Baymiller, Maxwell J"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Martinis, Susan A","Chen, Jie","Chen, Lin-Feng","Kalsotra, Auinash"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-22T22:24:55Z","subjects":["tRNA synthetases","alternative splicing"],"languages":["en","eng"],"rights":["Copyright 2022 Maxwell Baymiller"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/115713","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Martinis, Susan A","Chen, Jie","Chen, Lin-Feng","Kalsotra, Auinash"]},{"key":"dc:creator","label":"Author","values":["Baymiller, Maxwell J"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-05","2022-04-19"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"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 at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["tRNA synthetases","alternative splicing"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2022 Maxwell Baymiller"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/115713"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","The student, Maxwell Baymiller, accepted the attached license on 2022-04-18 at 12:42.","The student, Maxwell Baymiller, submitted this Dissertation for approval on 2022-04-18 at 12:54.","This Dissertation was approved for publication on 2022-04-19 at 20:10.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17750 on 2022-11-11 at 12:47:08","The aminoacyl-tRNA synthetases (aaRS) are ubiquitous and essential enzymes which set the genetic code by attaching amino acids to their cognate tRNAs. Many eukaryotic synthetases balance this key function with diverse roles in cell signaling. Alternative splicing has been proposed as a mechanism whereby aaRS may gain new functionality or be specified from their catalytic role towards alternate activities. Here, I discovered a leukocyte-specific exon-skipping event in human leucyl-tRNA synthetase (LARS) using long-read sequencing. This splice variant, LSV3, lacks all tRNA leucylation activity as skipping of LARS exon 20 causes a 71 amino acid deletion in the catalytic domain. However, LSV3 retains its role as a leucine sensor and signal transducer for the mammalian target of rapamycin (mTOR) pathway, even though the deletion includes a portion of the previously mapped Vps34-binding domain. I further found that expression of LSV3 is regulated by serine-arginine rich splicing factor 1 (SRSF1) in a cell type-specific manner, and this leads to increased exon skipping during immune cell activation and differentiation. Other alternative splicing events related to non-canonical functions of aaRS are controlled by SRSF1, including exon 2 skipping of tryptophanyl-tRNA synthetase (WARS), which induces its anti-angiogenic activity. I also identify a promising new modulator of the cell death inhibition function of glutaminyl-tRNA synthetase (QARS) via skipping of its exon 23. While when this QARS exon 23 skipping increases remains unclear, I found that LARS exon 20 skipping in LSV3 is greatly induced during cell death. Therefore, alternative splicing has provided functional specificity to the housekeeping LARS protein during cell death and immune signaling by separating its canonical and cell signaling roles."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulated alternative splicing separates canonical and cell signaling functions of aminoacyl-tRNA synthetases"]}]}],"canonical_facts":{"dc:contributor":["Martinis, Susan A","Chen, Jie","Chen, Lin-Feng","Kalsotra, Auinash"],"dc:creator":["Baymiller, Maxwell J"],"dc:date":["2022-05","2022-04-19"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-05-01","The student, Maxwell Baymiller, accepted the attached license on 2022-04-18 at 12:42.","The student, Maxwell Baymiller, submitted this Dissertation for approval on 2022-04-18 at 12:54.","This Dissertation was approved for publication on 2022-04-19 at 20:10.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17750 on 2022-11-11 at 12:47:08","The aminoacyl-tRNA synthetases (aaRS) are ubiquitous and essential enzymes which set the genetic code by attaching amino acids to their cognate tRNAs. Many eukaryotic synthetases balance this key function with diverse roles in cell signaling. Alternative splicing has been proposed as a mechanism whereby aaRS may gain new functionality or be specified from their catalytic role towards alternate activities. Here, I discovered a leukocyte-specific exon-skipping event in human leucyl-tRNA synthetase (LARS) using long-read sequencing. This splice variant, LSV3, lacks all tRNA leucylation activity as skipping of LARS exon 20 causes a 71 amino acid deletion in the catalytic domain. However, LSV3 retains its role as a leucine sensor and signal transducer for the mammalian target of rapamycin (mTOR) pathway, even though the deletion includes a portion of the previously mapped Vps34-binding domain. I further found that expression of LSV3 is regulated by serine-arginine rich splicing factor 1 (SRSF1) in a cell type-specific manner, and this leads to increased exon skipping during immune cell activation and differentiation. Other alternative splicing events related to non-canonical functions of aaRS are controlled by SRSF1, including exon 2 skipping of tryptophanyl-tRNA synthetase (WARS), which induces its anti-angiogenic activity. I also identify a promising new modulator of the cell death inhibition function of glutaminyl-tRNA synthetase (QARS) via skipping of its exon 23. While when this QARS exon 23 skipping increases remains unclear, I found that LARS exon 20 skipping in LSV3 is greatly induced during cell death. Therefore, alternative splicing has provided functional specificity to the housekeeping LARS protein during cell death and immune signaling by separating its canonical and cell signaling roles."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/115713"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Maxwell Baymiller"],"dc:subject":["tRNA synthetases","alternative splicing"],"dc:title":["Regulated alternative splicing separates canonical and cell signaling functions of aminoacyl-tRNA synthetases"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:55Z"}