{"id":"3123dd8b-8084-5268-96d1-d2f314906e52","stable_key":"availability:ftsj1-um34-impairment:2","predicate":"reduces_when_lost","statement":"Experimental cells lacking FTSJ1 become more sensitive to oxidative stress.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Cell/biochemical and animal xenograft; a narrow primary-study spot check supports the named FTSJ1 finding.","direction":"negative","is_public":true,"mechanism_event_id":"b47acd82-54f7-556a-91dd-b29ccd114531","mechanism_event_label":"Experimental cells lacking FTSJ1 become more sensitive to oxidative stress.","subject":{"id":"093683ad-836f-5f4e-8822-ea7915a38f52","slug":"ftsj1","display_name":"FTSJ1","entity_type_key":"protein"},"object":{"id":"856d4a95-da7b-58fe-92bb-7a1747f07c75","slug":"oxidative-stress-resistance","display_name":"Oxidative-stress resistance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b47acd82-54f7-556a-91dd-b29ccd114531","stable_key":"availability:ftsj1-um34-impairment:2","event_type":"availability_dependent_change","label":"Experimental cells lacking FTSJ1 become more sensitive to oxidative stress.","description":"Experimental loss of FTSJ1-dependent tRNA modification. Cell/biochemical studies and melanoma xenograft models reported in the 2024 FTSJ1 study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"093683ad-836f-5f4e-8822-ea7915a38f52","slug":"ftsj1","display_name":"FTSJ1","entity_type_key":"protein"},"role":"condition_input","stoichiometry":null,"state_label":"Experimental loss of FTSJ1-dependent tRNA modification.","sequence_order":0,"notes":""},{"entity":{"id":"856d4a95-da7b-58fe-92bb-7a1747f07c75","slug":"oxidative-stress-resistance","display_name":"Oxidative-stress resistance","entity_type_key":"cellular_process"},"role":"affected_component","stoichiometry":null,"state_label":"Experimental loss of FTSJ1-dependent tRNA modification.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Experimental loss of FTSJ1-dependent tRNA modification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Cell/biochemical studies and melanoma xenograft models reported in the 2024 FTSJ1 study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"FTSJ1 loss is a machinery perturbation, not itself a nutritional selenium-deficiency syndrome. The results do not prove that Um34 determines every selenoprotein phenotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"325f71b6-5cd6-57bc-a406-2e8603bfac60","evidence_kind":"source_passage","locator":"lines 75-75","start_line":75,"end_line":75,"excerpt":"Update: FTSJ1 was identified in 2024 as the tRNA^[Ser]Sec Um34 methyltransferase. Loss of FTSJ1 reduced efficient Sec insertion and sensitized experimental cells to oxidative stress. Evidence: cell/biochemical and melanoma xenograft models. [1]","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":"1b8ef6de-22a8-5742-96bd-5d80a1f84441","title":"Selective preservation is not a universal ranking by one modification","kind":"qualification","status":"qualified","why":"The earlier molecular draft says one ribose methylation continuously ranks about 25 proteins. The new reference describes multiple layers and tissue- and transcript-specific dependencies.","resolution":"Keep the unequal response pattern while qualifying its mechanism and ordering. Preserve the separately recorded isoform-label correction; do not silently replace it with a new universal assignment.","created_at":"2026-09-17 05:59:32","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/1b8ef6de-22a8-5742-96bd-5d80a1f84441","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1541,"end_line":1547,"papers":[{"paper_key":"carlson-2005","title":"Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA","url":"https://digitalcommons.unl.edu/biochemgladyshev/54/","doi":"10.1074/jbc.M411725200","year":2005,"model":"Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34","summary":"Selenoproteins differ in modification dependence; no universal two-class routing rule."},{"paper_key":"nease-2024","title":"Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis","url":"https://www.nature.com/articles/s43018-024-00844-8","doi":"10.1038/s43018-024-00844-8","year":2024,"model":"Biochemistry, human melanoma cells and mouse metastasis/xenograft models","summary":"Identifies FTSJ1 as the Sec-tRNA Um34 methyltransferase."}]},"sides":[{"conflict_id":"1b8ef6de-22a8-5742-96bd-5d80a1f84441","ordinal":0,"label":"Earlier statement","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":209,"end_line":209,"quote":"One ribose methylation on one tRNA continuously ranks \\~25 proteins by survival value. That is a startlingly compact resource-allocation algorithm implemented in a single chemical modification. If you're modeling cellular triage, this is the cleanest biological instance of it.","claim_id":null,"source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":[]},{"conflict_id":"1b8ef6de-22a8-5742-96bd-5d80a1f84441","ordinal":1,"label":"New reference qualification","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":11,"end_line":15,"quote":"Selenium deficiency is not just a shortage. It is a shortage with a hierarchy.\n\nAs selenium supply falls, selenoproteins do not decline equally. Selective regulation of tRNA modification, UGA recoding, SECIS-dependent translation, mRNA stability, and tissue-specific selenium transport means that some selenoproteins are more sensitive to selenium supply than others.\n\nThe hierarchy is real, but it is not one universal kill order implemented by a single switch. Different mechanisms contribute in different transcripts and tissues, and much of the fine-grained hierarchy comes from animal and cell models rather than validated plasma thresholds in humans.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]}]},{"id":"de957c1a-6439-5dd3-8149-06027ad575d5","title":"The formerly unassigned Um34 enzyme is identified as FTSJ1","kind":"contradiction","status":"corrected","why":"The earlier correction table lists the Um34 methylation enzyme as unassigned. The new reference identifies FTSJ1 and cites the 2024 experimental study.","resolution":"Record FTSJ1 as the identified tRNA[Ser]Sec Um34 methyltransferase, while keeping the earlier passage as a dated knowledge state and avoiding a nutritional diagnosis from FTSJ1 loss.","created_at":"2026-09-17 05:59:32","record_type":"correction","display_label":"Correction history","record_url":"/corrections/de957c1a-6439-5dd3-8149-06027ad575d5","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1549,"end_line":1554,"papers":[{"paper_key":"nease-2024","title":"Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis","url":"https://www.nature.com/articles/s43018-024-00844-8","doi":"10.1038/s43018-024-00844-8","year":2024,"model":"Biochemistry, human melanoma cells and mouse metastasis/xenograft models","summary":"Identifies FTSJ1 as the Sec-tRNA Um34 methyltransferase."}]},"sides":[{"conflict_id":"de957c1a-6439-5dd3-8149-06027ad575d5","ordinal":0,"label":"Earlier statement","revision_id":"4cec6304-35d7-5560-9133-e6ea689db838","start_line":153,"end_line":157,"quote":"| Position Mark Made by  |                        |                             |\n| ---------------------- | ---------------------- | --------------------------- |\n| A37                    | **i⁶A** (isopentenyl)  | TRIT1                       |\n| U34                    | cm⁵U → **mcm⁵U**       | Elongator (ELP1–6) → ALKBH8 |\n| U34 ribose             | **Um34** (2′-O-methyl) | the last unassigned step    |","claim_id":null,"source_key":"corrections","source_title":"Selenium corrections and deep dive","claim_ids":[]},{"conflict_id":"de957c1a-6439-5dd3-8149-06027ad575d5","ordinal":1,"label":"New reference qualification","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":73,"end_line":75,"quote":"Disrupting upstream tRNA modification in experimental models can selectively reduce proteins such as GPX1 and SELENOW while relatively preserving others. The exact dependency is protein- and model-specific, not a universal ranking of all ~25 human selenoproteins.\n\nUpdate: FTSJ1 was identified in 2024 as the tRNA^[Ser]Sec Um34 methyltransferase. Loss of FTSJ1 reduced efficient Sec insertion and sensitized experimental cells to oxidative stress. Evidence: cell/biochemical and melanoma xenograft models. [1]","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]}]}],"research":null}