{"id":{"repo_id":"maryland","oai_identifier":"oai:drum.lib.umd.edu:1903/12658"},"canonical_url":"https://search.dev.ndltd.org/etd/maryland/oai:drum.lib.umd.edu:1903/12658","repository":{"repo_id":"maryland","name":"University of Maryland","base_url":"https://api.drum.lib.umd.edu/server/oai/request"},"display":{"title":"Messenger RNA Destabilization by -1 Programmed Ribosomal Frameshifting","abstract":"Although first discovered in viruses, previous studies have identified programmed -1 ribosomal frameshifting (-1 PRF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. This work improves and extends the computational methods used to search for potential -1 PRF signals. It continues to examine four yeast -1 PRF signals and show that they promote significant mRNA destabilization through the nonsense mediated (NMD) and no-go (NGD) decay pathways. Yeast EST2 mRNA is highly unstable and contains up to five -1 PRF signals. Ablation of the -1 PRF signals or of NMD stabilizes this mRNA. These same computational methods identified an operational programmed -1 ribosomal frameshift (-1 PRF) signal in the human mRNA encoding CCR5. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay (NMD) pathway. CCR5-mediated -1 PRF is stimulated by at least two miRNAs, one of which is shown to directly interact with the CCR5 -1 PRF signal. Structural analyses reveal a complex and dynamic mRNA structure in the -1 PRF signal, suggesting structural plasticity as the underlying biophysical basis for regulation of -1 PRF.","abstract_html":"Although first discovered in viruses, previous studies have identified programmed -1 ribosomal frameshifting (-1 PRF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. This work improves and extends the computational methods used to search for potential -1 PRF signals. It continues to examine four yeast -1 PRF signals and show that they promote significant mRNA destabilization through the nonsense mediated (NMD) and no-go (NGD) decay pathways. Yeast EST2 mRNA is highly unstable and contains up to five -1 PRF signals. Ablation of the -1 PRF signals or of NMD stabilizes this mRNA. These same computational methods identified an operational programmed -1 ribosomal frameshift (-1 PRF) signal in the human mRNA encoding CCR5. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay (NMD) pathway. CCR5-mediated -1 PRF is stimulated by at least two miRNAs, one of which is shown to directly interact with the CCR5 -1 PRF signal. Structural analyses reveal a complex and dynamic mRNA structure in the -1 PRF signal, suggesting structural plasticity as the underlying biophysical basis for regulation of -1 PRF.","abstract_has_math":false,"creators":["Belew, Ashton Trey"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Cell Biology & Molecular Genetics","school":null,"contributors":[],"advisors":["Dinman, Jonathan D"],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-24T03:02:15Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1903/12658","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Dinman, Jonathan D"]},{"key":"dc:contributor.department","label":"Department","values":["Cell Biology & Molecular Genetics"]},{"key":"dc:creator","label":"Author","values":["Belew, Ashton Trey"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2012-07-07T05:51:02Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2012-07-07T05:51:02Z"]},{"key":"dc:date.issued","label":"Date","values":["2012"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1903/12658"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Although first discovered in viruses, previous studies have identified programmed -1 ribosomal frameshifting (-1 PRF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. This work improves and extends the computational methods used to search for potential -1 PRF signals. It continues to examine four yeast -1 PRF signals and show that they promote significant mRNA destabilization through the nonsense mediated (NMD) and no-go (NGD) decay pathways. Yeast EST2 mRNA is highly unstable and contains up to five -1 PRF signals. Ablation of the -1 PRF signals or of NMD stabilizes this mRNA. These same computational methods identified an operational programmed -1 ribosomal frameshift (-1 PRF) signal in the human mRNA encoding CCR5. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay (NMD) pathway. CCR5-mediated -1 PRF is stimulated by at least two miRNAs, one of which is shown to directly interact with the CCR5 -1 PRF signal. Structural analyses reveal a complex and dynamic mRNA structure in the -1 PRF signal, suggesting structural plasticity as the underlying biophysical basis for regulation of -1 PRF."]},{"key":"dc:title","label":"Title","values":["Messenger RNA Destabilization by -1 Programmed Ribosomal Frameshifting"]}]}],"canonical_facts":{"dc:contributor.advisor":["Dinman, Jonathan D"],"dc:contributor.department":["Cell Biology & Molecular Genetics"],"dc:creator":["Belew, Ashton Trey"],"dc:date.accessioned":["2012-07-07T05:51:02Z"],"dc:date.available":["2012-07-07T05:51:02Z"],"dc:date.issued":["2012"],"dc:description.abstract":["Although first discovered in viruses, previous studies have identified programmed -1 ribosomal frameshifting (-1 PRF) signals in eukaryotic genomic sequences, and suggested a role in mRNA stability. This work improves and extends the computational methods used to search for potential -1 PRF signals. It continues to examine four yeast -1 PRF signals and show that they promote significant mRNA destabilization through the nonsense mediated (NMD) and no-go (NGD) decay pathways. Yeast EST2 mRNA is highly unstable and contains up to five -1 PRF signals. Ablation of the -1 PRF signals or of NMD stabilizes this mRNA. These same computational methods identified an operational programmed -1 ribosomal frameshift (-1 PRF) signal in the human mRNA encoding CCR5. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay (NMD) pathway. CCR5-mediated -1 PRF is stimulated by at least two miRNAs, one of which is shown to directly interact with the CCR5 -1 PRF signal. Structural analyses reveal a complex and dynamic mRNA structure in the -1 PRF signal, suggesting structural plasticity as the underlying biophysical basis for regulation of -1 PRF."],"dc:identifier.uri":["http://hdl.handle.net/1903/12658"],"dc:title":["Messenger RNA Destabilization by -1 Programmed Ribosomal Frameshifting"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T03:02:15Z"}