{"id":"37799a1f-b220-555a-8e8d-ecd8505f6f95","stable_key":"availability:gpx1-translation-and-nmd:3","predicate":"can_reduce_abundance_of","statement":"NMD can lower GPX1 mRNA abundance during selenium deficiency in susceptible models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Animal model and cell/biochemical; supplied-source statements with a narrow primary-study spot check.","direction":"negative","is_public":true,"mechanism_event_id":"a19059e6-ba12-5dd7-bdce-e096135535ac","mechanism_event_label":"NMD can lower GPX1 mRNA abundance during selenium deficiency in susceptible models.","subject":{"id":"26640371-f0bc-53ff-8e95-bdf03b70fe49","slug":"nonsense-mediated-decay","display_name":"Nonsense-mediated mRNA decay","entity_type_key":"cellular_process"},"object":{"id":"2af2369e-e84b-5918-a27e-0387d268cf49","slug":"gpx1-mrna","display_name":"GPX1 mRNA","entity_type_key":"rna"},"evidence_count":2,"mechanism_event":{"id":"a19059e6-ba12-5dd7-bdce-e096135535ac","stable_key":"availability:gpx1-translation-and-nmd:3","event_type":"availability_dependent_change","label":"NMD can lower GPX1 mRNA abundance during selenium deficiency in susceptible models.","description":"Selenium restriction reduces recoding efficiency in an NMD-compatible GPX1 transcript context. Transcript-specific mechanism supported by animal and cell experiments, including rat hepatocytes and cultured-cell GPX1 studies.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"26640371-f0bc-53ff-8e95-bdf03b70fe49","slug":"nonsense-mediated-decay","display_name":"Nonsense-mediated mRNA decay","entity_type_key":"cellular_process"},"role":"condition_input","stoichiometry":null,"state_label":"Selenium restriction reduces recoding efficiency in an NMD-compatible GPX1 transcript context.","sequence_order":0,"notes":""},{"entity":{"id":"2af2369e-e84b-5918-a27e-0387d268cf49","slug":"gpx1-mrna","display_name":"GPX1 mRNA","entity_type_key":"rna"},"role":"affected_component","stoichiometry":null,"state_label":"Selenium restriction reduces recoding efficiency in an NMD-compatible GPX1 transcript context.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Selenium restriction reduces recoding efficiency in an NMD-compatible GPX1 transcript context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Transcript-specific mechanism supported by animal and cell experiments, including rat hepatocytes and cultured-cell GPX1 studies.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"NMD requires susceptible transcript architecture. It is not the fate of every selenoprotein transcript and has no established human plasma onset threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2c2b46a4-fa0b-512b-9567-b125883e5a8b","evidence_kind":"source_passage","locator":"lines 87-97","start_line":87,"end_line":97,"excerpt":"Layer 4 — nonsense-mediated decay (NMD). If a UGA is interpreted as termination in an NMD-compatible transcript architecture, the mRNA can be destabilized.\n\ninefficient UGA recoding\n        ↓\npremature termination in a susceptible transcript\n        ↓\nNMD machinery engaged\n        ↓\nselenoprotein mRNA abundance falls\n\nFor transcripts such as GPX1, selenium deficiency can therefore reduce expression at more than one level: translation efficiency and mRNA abundance. That is stronger than simple proportional substrate limitation, but it is still transcript-specific.","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}},{"id":"5e14c14f-8e04-5d6e-9519-4b60cd5a8e4e","evidence_kind":"source_passage","locator":"lines 287-293","start_line":287,"end_line":293,"excerpt":"GPX1 activity ↓\n\nOften strongly selenium-responsive\n\nGPX1 mRNA ↓ in susceptible models\n\nNMD can contribute","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}}],"relations":[],"conflicts":[],"corrections":[],"research":null}