{"id":{"repo_id":"umn","oai_identifier":"oai:conservancy.umn.edu:11299/198984"},"canonical_url":"https://search.dev.ndltd.org/etd/umn/oai:conservancy.umn.edu:11299/198984","repository":{"repo_id":"umn","name":"University of Minnesota","base_url":"https://conservancy.umn.edu/server/oai/request"},"display":{"title":"Deciphering the mechanism of Transferrin Receptor mRNA degradation under iron replete conditions","abstract":"Iron is an essential co-factor required for many biochemical reactions in our body, however iron overload can be detrimental to the cells. Thus, intra-cellular iron concentration is meticulously controlled. For most cells in the body, the transferrin receptor (TFRC-1) is the major means through which iron is imported into the cell. Influx of transferrin bound iron is regulated by changes in the stability of TFRC-1 mRNA. Under iron deplete conditions, iron regulatory proteins 1 and 2 (IRP-1 & 2) bind to specific sequence elements within the 3’ untranslated region (3’UTR) of the TFRC-1 mRNA and prevent its degradation. Whereas under iron replete conditions there is minimal binding between the IRPs and TFRC-1 mRNA, resulting in TFRC-1 mRNA degradation, the precise mechanism of which is yet unknown. This study was based on three hypotheses that could lead to identification of the mechanism of TFRC-1 mRNA degradation. First, there could be a microRNA mediated silencing of the TFRC-1 mRNA. Secondly, the TFRC-1 mRNA could catalyse its own degradation or lastly an iron responsive endonuclease could degrade the TFRC-1 mRNA. Using a luciferase reporter system, we have performed a detailed mutagenesis study of a previously minimized TFRC-1 construct and identified three critical elements for degradation. The three elements impart a graded response to stability and a similar graded response is also observed in endogenous TFRC-1 mRNA under certain conditions. Results from the mutagenesis study strongly suggest that an unidentified endonuclease is responsible for degradation. Identifying this endonuclease will provide a novel therapeutic target to manipulate iron concentration in pathological cells.","abstract_html":"Iron is an essential co-factor required for many biochemical reactions in our body, however iron overload can be detrimental to the cells. Thus, intra-cellular iron concentration is meticulously controlled. For most cells in the body, the transferrin receptor (TFRC-1) is the major means through which iron is imported into the cell. Influx of transferrin bound iron is regulated by changes in the stability of TFRC-1 mRNA. Under iron deplete conditions, iron regulatory proteins 1 and 2 (IRP-1 & 2) bind to specific sequence elements within the 3’ untranslated region (3’UTR) of the TFRC-1 mRNA and prevent its degradation. Whereas under iron replete conditions there is minimal binding between the IRPs and TFRC-1 mRNA, resulting in TFRC-1 mRNA degradation, the precise mechanism of which is yet unknown. This study was based on three hypotheses that could lead to identification of the mechanism of TFRC-1 mRNA degradation. First, there could be a microRNA mediated silencing of the TFRC-1 mRNA. Secondly, the TFRC-1 mRNA could catalyse its own degradation or lastly an iron responsive endonuclease could degrade the TFRC-1 mRNA. Using a luciferase reporter system, we have performed a detailed mutagenesis study of a previously minimized TFRC-1 construct and identified three critical elements for degradation. The three elements impart a graded response to stability and a similar graded response is also observed in endogenous TFRC-1 mRNA under certain conditions. Results from the mutagenesis study strongly suggest that an unidentified endonuclease is responsible for degradation. Identifying this endonuclease will provide a novel therapeutic target to manipulate iron concentration in pathological cells.","abstract_has_math":false,"creators":["Rupani, Dhwani"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-05","date_published":"2016-05","updated_at":"2026-07-24T05:20:03Z","subjects":["critical elements","degradation","Transferrin receptor mRNA"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11299/198984","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Rupani, Dhwani"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-08-14T19:29:30Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-08-14T19:29:30Z"]},{"key":"dc:date.issued","label":"Date","values":["2016-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["critical elements","degradation","Transferrin receptor mRNA"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11299/198984"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["University of Minnesota M.S. thesis. May 2016. Major: Pharmacology. Advisor: Gregory Connell. 1 computer file (PDF); vi, 46 pages."]},{"key":"dc:description.abstract","label":"Abstract","values":["Iron is an essential co-factor required for many biochemical reactions in our body, however iron overload can be detrimental to the cells. Thus, intra-cellular iron concentration is meticulously controlled. For most cells in the body, the transferrin receptor (TFRC-1) is the major means through which iron is imported into the cell. Influx of transferrin bound iron is regulated by changes in the stability of TFRC-1 mRNA. Under iron deplete conditions, iron regulatory proteins 1 and 2 (IRP-1 & 2) bind to specific sequence elements within the 3’ untranslated region (3’UTR) of the TFRC-1 mRNA and prevent its degradation. Whereas under iron replete conditions there is minimal binding between the IRPs and TFRC-1 mRNA, resulting in TFRC-1 mRNA degradation, the precise mechanism of which is yet unknown. This study was based on three hypotheses that could lead to identification of the mechanism of TFRC-1 mRNA degradation. First, there could be a microRNA mediated silencing of the TFRC-1 mRNA. Secondly, the TFRC-1 mRNA could catalyse its own degradation or lastly an iron responsive endonuclease could degrade the TFRC-1 mRNA. Using a luciferase reporter system, we have performed a detailed mutagenesis study of a previously minimized TFRC-1 construct and identified three critical elements for degradation. The three elements impart a graded response to stability and a similar graded response is also observed in endogenous TFRC-1 mRNA under certain conditions. Results from the mutagenesis study strongly suggest that an unidentified endonuclease is responsible for degradation. Identifying this endonuclease will provide a novel therapeutic target to manipulate iron concentration in pathological cells."]},{"key":"dc:title","label":"Title","values":["Deciphering the mechanism of Transferrin Receptor mRNA degradation under iron replete conditions"]}]}],"canonical_facts":{"dc:creator":["Rupani, Dhwani"],"dc:date.accessioned":["2018-08-14T19:29:30Z"],"dc:date.available":["2018-08-14T19:29:30Z"],"dc:date.issued":["2016-05"],"dc:description":["University of Minnesota M.S. thesis. May 2016. Major: Pharmacology. Advisor: Gregory Connell. 1 computer file (PDF); vi, 46 pages."],"dc:description.abstract":["Iron is an essential co-factor required for many biochemical reactions in our body, however iron overload can be detrimental to the cells. Thus, intra-cellular iron concentration is meticulously controlled. For most cells in the body, the transferrin receptor (TFRC-1) is the major means through which iron is imported into the cell. Influx of transferrin bound iron is regulated by changes in the stability of TFRC-1 mRNA. Under iron deplete conditions, iron regulatory proteins 1 and 2 (IRP-1 & 2) bind to specific sequence elements within the 3’ untranslated region (3’UTR) of the TFRC-1 mRNA and prevent its degradation. Whereas under iron replete conditions there is minimal binding between the IRPs and TFRC-1 mRNA, resulting in TFRC-1 mRNA degradation, the precise mechanism of which is yet unknown. This study was based on three hypotheses that could lead to identification of the mechanism of TFRC-1 mRNA degradation. First, there could be a microRNA mediated silencing of the TFRC-1 mRNA. Secondly, the TFRC-1 mRNA could catalyse its own degradation or lastly an iron responsive endonuclease could degrade the TFRC-1 mRNA. Using a luciferase reporter system, we have performed a detailed mutagenesis study of a previously minimized TFRC-1 construct and identified three critical elements for degradation. The three elements impart a graded response to stability and a similar graded response is also observed in endogenous TFRC-1 mRNA under certain conditions. Results from the mutagenesis study strongly suggest that an unidentified endonuclease is responsible for degradation. Identifying this endonuclease will provide a novel therapeutic target to manipulate iron concentration in pathological cells."],"dc:identifier.uri":["http://hdl.handle.net/11299/198984"],"dc:language.iso":["en"],"dc:subject":["critical elements","degradation","Transferrin receptor mRNA"],"dc:title":["Deciphering the mechanism of Transferrin Receptor mRNA degradation under iron replete conditions"],"dc:type":["Thesis or Dissertation"]},"updated_at":"2026-07-24T05:20:03Z"}