{"id":"677018da-5f9d-5919-93c4-1047e96ec08d","stable_key":"availability:limited-selenium-sec-trna:2","predicate":"can_limit","statement":"A constrained Sec-tRNA supply can impair selenocysteine insertion at UGA in a transcript-dependent manner.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Cell/biochemical mechanism; source-derived unverified synthesis.","direction":"negative","is_public":true,"mechanism_event_id":"3391b20e-30ba-59b0-86ef-56ad5918bb35","mechanism_event_label":"A constrained Sec-tRNA supply can impair selenocysteine insertion at UGA in a transcript-dependent manner.","subject":{"id":"15ce9978-f9e2-528c-8a2f-1079154b5383","slug":"sec-trna","display_name":"Sec-tRNA[Ser]Sec","entity_type_key":"rna"},"object":{"id":"f71fba83-929f-5773-81f5-1796d8e5a369","slug":"uga-recoding","display_name":"UGA recoding","entity_type_key":"cellular_process"},"evidence_count":2,"mechanism_event":{"id":"3391b20e-30ba-59b0-86ef-56ad5918bb35","stable_key":"availability:limited-selenium-sec-trna:2","event_type":"availability_dependent_change","label":"A constrained Sec-tRNA supply can impair selenocysteine insertion at UGA in a transcript-dependent manner.","description":"Selenium intake or availability becomes inadequate for the cellular context. Biochemical pathway and experimental shortage model; effects depend on transcript and tissue.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"15ce9978-f9e2-528c-8a2f-1079154b5383","slug":"sec-trna","display_name":"Sec-tRNA[Ser]Sec","entity_type_key":"rna"},"role":"condition_input","stoichiometry":null,"state_label":"Selenium intake or availability becomes inadequate for the cellular context.","sequence_order":0,"notes":""},{"entity":{"id":"f71fba83-929f-5773-81f5-1796d8e5a369","slug":"uga-recoding","display_name":"UGA recoding","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Selenium intake or availability becomes inadequate for the cellular context.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Selenium intake or availability becomes inadequate for the cellular context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Biochemical pathway and experimental shortage model; effects depend on transcript and tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is a conditional supply constraint, not a prediction that all selenoproteins fall equally. No validated plasma cutoff is assigned.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f09139de-c458-5f34-a8d6-a9910d6df1c1","evidence_kind":"source_passage","locator":"lines 35-45","start_line":35,"end_line":45,"excerpt":"                                   Sec-tRNA^[Ser]Sec\n                                           ↓ eEFSec\n                              ribosome reaches UGA\n                                           ↓\n                        SECIS + SECISBP2/SBP2 machinery\n                                           ↓\n                              SELENOCYSTEINE INSERTED\n\nSerRS charging tRNA^[Ser]Sec with serine is an obligatory biosynthetic step, not a mistake. SEPHS2 supplies selenophosphate, while PSTK and SEPSECS convert the serine-charged tRNA into Sec-tRNA^[Ser]Sec.\n\nUGA recoding is intrinsically less straightforward than ordinary amino-acid insertion and its efficiency varies substantially by transcript and cellular context. It should not be treated as a universal 5–10% process across all selenoprotein mRNAs.","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":"a7cc611c-beeb-5045-a6b7-c1f1f71df197","evidence_kind":"source_passage","locator":"lines 783-790","start_line":783,"end_line":790,"excerpt":"selenium intake / availability ↓\n        │\n        ▼\ncentral selenium metabolism and Sec-tRNA supply become constrained\n        │\n        ├─ tRNA^[Ser]Sec modification can shift (including Um34 / FTSJ1 biology)\n        ├─ SECIS-dependent UGA recoding changes\n        ├─ selected transcripts can undergo stronger repression / NMD","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":[{"id":"2c57c4ac-75e2-5d18-81f0-09bcb5ededde","title":"SEPSECS uses selenium from selenophosphate, not intact selenophosphate substitution","kind":"contradiction","status":"corrected","why":"The phosphate-for-selenophosphate wording gives the wrong product. SerRS charging is an obligatory precursor step, not an aminoacylation error.","resolution":"Record phosphate elimination/selenium donation; retain the later correction of the mischarging interpretation.","created_at":"2026-09-17 07:19:34","record_type":"correction","display_label":"Correction history","record_url":"/corrections/2c57c4ac-75e2-5d18-81f0-09bcb5ededde","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1511,"end_line":1516,"papers":[{"paper_key":"palioura-2009","title":"The human SepSecS–tRNASec complex reveals mechanism of selenocysteine formation","url":"https://pubmed.ncbi.nlm.nih.gov/19608919/","doi":"10.1126/science.1173755","year":2009,"model":"Human enzyme/tRNA crystallography and biochemical assays","summary":"Selenophosphate supplies selenium rather than being incorporated intact."}]},"sides":[{"conflict_id":"2c57c4ac-75e2-5d18-81f0-09bcb5ededde","ordinal":0,"label":"Original preserved statement","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":16,"end_line":18,"quote":"3. **SerRS** mischarges tRNA^[Ser]Sec with plain **serine**. Wrong amino acid, on purpose.\n4. **PSTK** phosphorylates it → **O-phosphoseryl-tRNA**.\n5. **SepSecS** swaps the phosphate for selenophosphate → **Sec-tRNA^[Ser]Sec**. (Fun aside: SepSecS is the SLA/LP autoantigen in autoimmune hepatitis. Your immune system attacking the selenium machine.)","claim_id":null,"source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":[]},{"conflict_id":"2c57c4ac-75e2-5d18-81f0-09bcb5ededde","ordinal":1,"label":"Original preserved statement","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":43,"end_line":43,"quote":"SerRS charging tRNA^[Ser]Sec with serine is an obligatory biosynthetic step, not a mistake. SEPHS2 supplies selenophosphate, while PSTK and SEPSECS convert the serine-charged tRNA into Sec-tRNA^[Ser]Sec.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]},{"conflict_id":"2c57c4ac-75e2-5d18-81f0-09bcb5ededde","ordinal":2,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1511,"end_line":1516,"quote":"## SEPSECS uses selenium from selenophosphate, not intact selenophosphate substitution\n\nThe phosphate-for-selenophosphate wording gives the wrong product. SerRS charging is an obligatory precursor step, not an aminoacylation error.\n\nRecord phosphate elimination/selenium donation; retain the later correction of the mischarging interpretation.\nPrimary reference: [The human SepSecS–tRNASec complex reveals mechanism of selenocysteine formation](https://pubmed.ncbi.nlm.nih.gov/19608919/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]},{"id":"72ecddac-faf6-5af4-9cac-9ef792ff63d3","title":"UGA recoding does not have a universal 5–10 percent efficiency","kind":"qualification","status":"qualified","why":"Reporter/lysate efficiencies cannot establish premature termination for most endogenous translation; 95 percent efficiency still permits downward regulatory range.","resolution":"Retain transcript/condition-specific measurements; remove mathematical necessity and untested adaptive explanation. Later deficiency source already qualifies this.","created_at":"2026-09-17 07:19:34","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/72ecddac-faf6-5af4-9cac-9ef792ff63d3","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1556,"end_line":1561,"papers":[{"paper_key":"secis-2009","title":"Novel structural determinants in human SECIS elements modulate the translational recoding of UGA as selenocysteine","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2761289/","doi":"10.1093/nar/gkp635","year":2009,"model":"26 human SECIS reporters in HEK293/HepG2 and cell-free translation","summary":"Large element-dependent differences preclude a universal endogenous efficiency inference."}]},"sides":[{"conflict_id":"72ecddac-faf6-5af4-9cac-9ef792ff63d3","ordinal":0,"label":"Original preserved statement","revision_id":"4cec6304-35d7-5560-9133-e6ea689db838","start_line":192,"end_line":192,"quote":"Baseline Sec insertion efficiency is shockingly bad — **roughly 5–10%** at a typical UGA. Most ribosomes on a selenoprotein mRNA terminate early. **This inefficiency is the feature**: it's what makes the system tunable at all. A process running at 95% efficiency has no dynamic range.","claim_id":null,"source_key":"corrections","source_title":"Selenium corrections and deep dive","claim_ids":[]},{"conflict_id":"72ecddac-faf6-5af4-9cac-9ef792ff63d3","ordinal":1,"label":"Original preserved statement","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":45,"end_line":45,"quote":"UGA recoding is intrinsically less straightforward than ordinary amino-acid insertion and its efficiency varies substantially by transcript and cellular context. It should not be treated as a universal 5–10% process across all selenoprotein mRNAs.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]},{"conflict_id":"72ecddac-faf6-5af4-9cac-9ef792ff63d3","ordinal":2,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1556,"end_line":1561,"quote":"## UGA recoding does not have a universal 5–10 percent efficiency\n\nReporter/lysate efficiencies cannot establish premature termination for most endogenous translation; 95 percent efficiency still permits downward regulatory range.\n\nRetain transcript/condition-specific measurements; remove mathematical necessity and untested adaptive explanation. Later deficiency source already qualifies this.\nPrimary reference: [Novel structural determinants in human SECIS elements modulate the translational recoding of UGA as selenocysteine](https://pmc.ncbi.nlm.nih.gov/articles/PMC2761289/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":null}