{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/120483"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/120483","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Regulation of Salmonella pathogenicity island I through the hilD mRNA 3' untranslated region","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2025-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2025-05-01","abstract_has_math":false,"creators":["Abdulla, Sabrina Zahir"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Microbiology","degree_department":null,"school":null,"contributors":["Vanderpool, Carin K","Slauch, James M","Metcalf, William W","Kuzminov, Andrei"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-05","date_published":"2023-05","updated_at":"2026-07-22T22:24:57Z","subjects":["Salmonella","Pathogenicity","Spi-1","Srnas"],"languages":["en","eng"],"rights":["Copyright 2023 Sabrina Abdulla"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/120483","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Vanderpool, Carin K","Slauch, James M","Metcalf, William W","Kuzminov, Andrei"]},{"key":"dc:creator","label":"Author","values":["Abdulla, Sabrina Zahir"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2023-05","2023-01-17"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology"]},{"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":["Salmonella","Pathogenicity","Spi-1","Srnas"]}]},{"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 2023 Sabrina Abdulla"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/120483"]}]},{"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 2025-05-01","The student, Sabrina Abdulla, accepted the attached license on 2023-01-12 at 14:13.","The student, Sabrina Abdulla, submitted this Dissertation for approval on 2023-01-12 at 14:20.","This Dissertation was approved for publication on 2023-01-17 at 15:19.","DSpace SAF Submission Ingestion Package generated from Vireo submission #18822 on 2023-09-01 at 17:18:57","Salmonella enterica serovar Typhimurium is an enteric pathogen associated with food-borne disease. Salmonella invades the intestinal epithelium using a type three secretion system encoded on Salmonella pathogenicity Island 1 (SPI-1). SPI-1 genes are tightly regulated by a complex feed-forward loop to ensure proper spatial and temporal expression. Most regulatory input is integrated at HilD, through control of hilD mRNA translation or HilD protein activity. The hilD mRNA possesses a 310-nucleotide 3′ untranslated region (UTR) that influences HilD and SPI-1 expression, and this regulation is dependent on Hfq and RNase E, cofactors known to mediate small RNA (sRNA) activities. Thus, we hypothesized that the hilD mRNA 3′ UTR is a target for sRNAs. Here we show that the sRNAs, SdsR and Spot 42, regulate SPI-1 by targeting different regions of the hilD mRNA 3′ UTR. Regulatory activities of these sRNAs depend on Hfq and RNase E, in agreement with previous roles found for both at the hilD 3′ UTR. Salmonella mutants lacking SdsR and Spot 42 have decreased virulence in a mouse model of infection. Collectively, this work suggests that these sRNAs targeting the hilD mRNA 3′ UTR increase hilD mRNA levels by interfering with RNase E-dependent mRNA degradation and that this regulatory effect is required for Salmonella invasiveness. Further, we identify a role for Rho and NusG at the hilD mRNA 3′UTR. Previous work has identified that Gre factors are essential to allow for proper hilD expression. Here, we identify that Gre factors are only required when Rho is functional, implicating a mechanism where Gre factors helps bypass premature termination by Rho during SPI-1 permissive conditions. In addition, we find that there is interplay between Rho, RNase E and SdsR, providing new insight into the mechanism by which the hilD mRNA 3′ UTR functions as a regulatory module. Our work provides novel insights into mechanisms of sRNA regulation at bacterial mRNA 3′ UTRs, and adds to our knowledge of post-transcriptional regulation and transcription termination as a means of regulating the SPI-1 complex feed-forward loop."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulation of Salmonella pathogenicity island I through the hilD mRNA 3' untranslated region"]}]}],"canonical_facts":{"dc:contributor":["Vanderpool, Carin K","Slauch, James M","Metcalf, William W","Kuzminov, Andrei"],"dc:creator":["Abdulla, Sabrina Zahir"],"dc:date":["2023-05","2023-01-17"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2025-05-01","The student, Sabrina Abdulla, accepted the attached license on 2023-01-12 at 14:13.","The student, Sabrina Abdulla, submitted this Dissertation for approval on 2023-01-12 at 14:20.","This Dissertation was approved for publication on 2023-01-17 at 15:19.","DSpace SAF Submission Ingestion Package generated from Vireo submission #18822 on 2023-09-01 at 17:18:57","Salmonella enterica serovar Typhimurium is an enteric pathogen associated with food-borne disease. Salmonella invades the intestinal epithelium using a type three secretion system encoded on Salmonella pathogenicity Island 1 (SPI-1). SPI-1 genes are tightly regulated by a complex feed-forward loop to ensure proper spatial and temporal expression. Most regulatory input is integrated at HilD, through control of hilD mRNA translation or HilD protein activity. The hilD mRNA possesses a 310-nucleotide 3′ untranslated region (UTR) that influences HilD and SPI-1 expression, and this regulation is dependent on Hfq and RNase E, cofactors known to mediate small RNA (sRNA) activities. Thus, we hypothesized that the hilD mRNA 3′ UTR is a target for sRNAs. Here we show that the sRNAs, SdsR and Spot 42, regulate SPI-1 by targeting different regions of the hilD mRNA 3′ UTR. Regulatory activities of these sRNAs depend on Hfq and RNase E, in agreement with previous roles found for both at the hilD 3′ UTR. Salmonella mutants lacking SdsR and Spot 42 have decreased virulence in a mouse model of infection. Collectively, this work suggests that these sRNAs targeting the hilD mRNA 3′ UTR increase hilD mRNA levels by interfering with RNase E-dependent mRNA degradation and that this regulatory effect is required for Salmonella invasiveness. Further, we identify a role for Rho and NusG at the hilD mRNA 3′UTR. Previous work has identified that Gre factors are essential to allow for proper hilD expression. Here, we identify that Gre factors are only required when Rho is functional, implicating a mechanism where Gre factors helps bypass premature termination by Rho during SPI-1 permissive conditions. In addition, we find that there is interplay between Rho, RNase E and SdsR, providing new insight into the mechanism by which the hilD mRNA 3′ UTR functions as a regulatory module. Our work provides novel insights into mechanisms of sRNA regulation at bacterial mRNA 3′ UTRs, and adds to our knowledge of post-transcriptional regulation and transcription termination as a means of regulating the SPI-1 complex feed-forward loop."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/120483"],"dc:language":["en","eng"],"dc:rights":["Copyright 2023 Sabrina Abdulla"],"dc:subject":["Salmonella","Pathogenicity","Spi-1","Srnas"],"dc:title":["Regulation of Salmonella pathogenicity island I through the hilD mRNA 3' untranslated region"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Microbiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:57Z"}