{"id":"17de7b28-039f-5f7c-b34d-325181b45aed","stable_key":"research:um34-selective","predicate":"supports_efficient_expression_of","statement":"Sec-tRNA Um34 modification contributes to efficient expression of selected stress-responsive selenoproteins including GPX1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"context_dependent","is_public":true,"mechanism_event_id":"189b28e3-554a-5243-a832-c19b28f3491e","mechanism_event_label":"This tRNA modification helps make some selenium proteins more than others.","subject":{"id":"028e853c-7b1d-5be4-acdd-1c6a84a81b98","slug":"mcm5um34","display_name":"mcm5Um34","entity_type_key":"rna_modification"},"object":{"id":"e79d035c-0c02-5c0e-ac8f-d7fdeb663fbd","slug":"gpx1","display_name":"GPX1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"189b28e3-554a-5243-a832-c19b28f3491e","stable_key":"research:um34-selective","event_type":"contextual_mechanism","label":"This tRNA modification helps make some selenium proteins more than others.","description":"Sec-tRNA Um34 modification contributes to efficient expression of selected stress-responsive selenoproteins including GPX1.","status":"active","compartment":null,"participants":[{"entity":{"id":"028e853c-7b1d-5be4-acdd-1c6a84a81b98","slug":"mcm5um34","display_name":"mcm5Um34","entity_type_key":"rna_modification"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e79d035c-0c02-5c0e-ac8f-d7fdeb663fbd","slug":"gpx1","display_name":"GPX1","entity_type_key":"protein"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Mouse tissues and human melanoma cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34; Biochemistry, human melanoma cells and mouse metastasis/xenograft models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Older tRNA mutant also affects i6A37; no universal exclusive stress/housekeeping routing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus and Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f830f5c3-5a91-519a-98f2-9de63999ec7b","evidence_kind":"curated_literature_summary","locator":"lines 1178-1189","start_line":1178,"end_line":1189,"excerpt":"## um34-selective\n\nThis tRNA modification helps make some selenium proteins more than others.\n\nSec-tRNA Um34 modification contributes to efficient expression of selected stress-responsive selenoproteins including GPX1.\n\nOrganism: Mus musculus and Homo sapiens\nCell type: Mouse tissues and human melanoma cells\nExperimental model: Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34; Biochemistry, human melanoma cells and mouse metastasis/xenograft models\nLimitations: Older tRNA mutant also affects i6A37; no universal exclusive stress/housekeeping routing.\nPrimary reference: [Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA](https://digitalcommons.unl.edu/biochemgladyshev/54/)\nPrimary reference: [Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis](https://www.nature.com/articles/s43018-024-00844-8)","model_system":"Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34; Biochemistry, human melanoma cells and mouse metastasis/xenograft models","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"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":"c6f5fc60-d928-581c-87d0-15e0abf2889f","title":"mcm5u34: corrected tRNA isoform labels","kind":"label_reversal","status":"corrected","why":"The earlier draft reversed the two tRNA isoform labels. The author explicitly corrected that error. This is correction history, not an unresolved scientific disagreement.","resolution":"The reversed assignment is superseded. Both source versions remain available in correction history. The later literature review qualifies the replacement wording: modification dependence varies by selenoprotein and experimental context; the two isoforms do not establish a universal housekeeping-versus-stress routing rule.","created_at":"2026-09-17 05:16:58","record_type":"correction","display_label":"Correction history","record_url":"/corrections/c6f5fc60-d928-581c-87d0-15e0abf2889f","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1525,"end_line":1531,"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":"c6f5fc60-d928-581c-87d0-15e0abf2889f","ordinal":0,"label":"Original assignment","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":30,"end_line":30,"quote":"- **mcm⁵U** — the \"stress\" form","source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":["8d435309-f139-5602-9f77-6a5c5beacea0"]},{"conflict_id":"c6f5fc60-d928-581c-87d0-15e0abf2889f","ordinal":1,"label":"Explicit source correction","revision_id":"4cec6304-35d7-5560-9133-e6ea689db838","start_line":5,"end_line":5,"quote":"- **mcm⁵U34** (no ribose methyl) → supports **housekeeping** selenoproteins: TXNRD1, GPX4","source_key":"corrections","source_title":"Selenium corrections and deep dive","claim_ids":["bf75305d-1e89-54bb-a3aa-c7cc6ccfc587"]}]},{"id":"65467447-6d61-57f2-b75f-d3098ddeb1e8","title":"mcm5um34: corrected tRNA isoform labels","kind":"label_reversal","status":"corrected","why":"The earlier draft reversed the two tRNA isoform labels. The author explicitly corrected that error. This is correction history, not an unresolved scientific disagreement.","resolution":"The reversed assignment is superseded. Both source versions remain available in correction history. The later literature review qualifies the replacement wording: modification dependence varies by selenoprotein and experimental context; the two isoforms do not establish a universal housekeeping-versus-stress routing rule.","created_at":"2026-09-17 05:16:58","record_type":"correction","display_label":"Correction history","record_url":"/corrections/65467447-6d61-57f2-b75f-d3098ddeb1e8","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1533,"end_line":1539,"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":"65467447-6d61-57f2-b75f-d3098ddeb1e8","ordinal":0,"label":"Original assignment","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":31,"end_line":31,"quote":"- **mcm⁵Um** — 2′-O-methylribose added. The \"housekeeping\" form.","source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":["02da9a25-f443-513e-bfcc-654d8b4d26f6"]},{"conflict_id":"65467447-6d61-57f2-b75f-d3098ddeb1e8","ordinal":1,"label":"Explicit source correction","revision_id":"4cec6304-35d7-5560-9133-e6ea689db838","start_line":6,"end_line":6,"quote":"- **mcm⁵Um34** (ribose methylated) → **required** for the **stress-related** set: GPX1, SELENOW","source_key":"corrections","source_title":"Selenium corrections and deep dive","claim_ids":["e7e8040f-092d-59e7-b31e-4b095d7019e4"]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"This tRNA modification helps make some selenium proteins more than others.","evidence_scope":"direct_experimental","papers":[{"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."},{"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."}]}}