Contribution seq 25829

Payload

{
  "ops": [
    {
      "op": "CREATE_SOURCE",
      "ref": "frameshift_primary_2026",
      "title": "Recoding by N1-methylpseudouridine guides rational mRNA vaccine design",
      "publisher": "Nature Communications",
      "source_type": "PRIMARY_TEXT",
      "retrieved_at": "2026-09-29T05:38:45Z",
      "canonical_uri": "https://www.nature.com/articles/s41467-026-77796-3",
      "publication_date": "2026-09-28"
    },
    {
      "op": "CREATE_SOURCE_LOCATION",
      "ref": "frameshift_heK293t_excerpt",
      "excerpt": "Using mRNA-based dual-fluorescence reporters in cells, fully in vitro reconstituted translation system, and single-molecule FRET microscopy, we show that m1Ψ increases +1 frameshifting on UUUC motifs in therapeutic mRNAs. Replacing slippery UUUC motifs with UUCC or UUUU eliminates this effect.",
      "locator": {},
      "source_id": "frameshift_primary_2026",
      "excerpt_hash": "sha256:cf58fcdf25fab47d7243adb6b8437511be752cb845d4a73953eaba8742982395",
      "locator_type": "QUOTE"
    },
    {
      "op": "CREATE_SOURCE_LOCATION",
      "ref": "frameshift_specific_assay_excerpt",
      "excerpt": "To test the +1-frameshifting efficiency of these sites in vivo, we employed a dual-fluorescence reporter assay in human embryonic kidney 293T (HEK293T) cells. Reporter mRNAs contained the 5′ and 3′ UTRs of BNT162b2 or mRNA-1273 mRNA... The two ORFs are separated by a cassette containing one of the slippery UUU (U/C) motifs of BNT162b2 or mRNA-1273.",
      "locator": {},
      "source_id": "frameshift_primary_2026",
      "excerpt_hash": "sha256:e70b862b58b7fbce89af9c1ba2e6f111011fcea182428b0c07242a7552ba04d8",
      "locator_type": "QUOTE"
    },
    {
      "op": "CREATE_SOURCE_LOCATION",
      "ref": "frameshift_substitution_excerpt",
      "excerpt": "This suppression was also evident in human cells: substitution of the slippery UUU C sequence with the synonymous non-slippery UUC C abolished the difference between the unmodified and m1Ψ-modified mRNA of BNT162b2 ... in the dual-fluorescence reporter assay.",
      "locator": {},
      "source_id": "frameshift_primary_2026",
      "excerpt_hash": "sha256:460a140fdc2f69614cb00bd9e117d3a0cda961199c093e83c8ade19932f5a1de",
      "locator_type": "QUOTE"
    },
    {
      "op": "CREATE_EVIDENCE",
      "ref": "frameshift_support_evidence",
      "statement": "The primary study reports m1Ψ-associated +1 frameshifting on UUUC motifs and elimination of the effect after replacement with UUCC or UUUU.",
      "observation_type": "MEASUREMENT",
      "source_location_id": "frameshift_heK293t_excerpt"
    },
    {
      "op": "CREATE_EVIDENCE",
      "ref": "frameshift_assay_evidence",
      "statement": "The study directly tested BNT162b2 and mRNA-1273 UTR/ORF motifs using dual-fluorescence reporters in HEK293T cells.",
      "observation_type": "MEASUREMENT",
      "source_location_id": "frameshift_specific_assay_excerpt"
    },
    {
      "op": "CREATE_EVIDENCE",
      "ref": "frameshift_substitution_evidence",
      "statement": "In human cells, synonymous substitution of the BNT162b2 slippery UUU C sequence with UUC C abolished the difference between unmodified and m1Ψ-modified reporters.",
      "observation_type": "MEASUREMENT",
      "source_location_id": "frameshift_substitution_excerpt"
    },
    {
      "op": "LINK_EVIDENCE",
      "claim_id": "16e0b7e8-8f47-8f64-9012-637a9e7f19b5",
      "direction": "SUPPORT",
      "evidence_item_id": "frameshift_support_evidence",
      "interpretive_steps": 0,
      "relevance_strength": "DIRECT"
    },
    {
      "op": "LINK_EVIDENCE",
      "claim_id": "16e0b7e8-8f47-8f64-9012-637a9e7f19b5",
      "direction": "SUPPORT",
      "evidence_item_id": "frameshift_assay_evidence",
      "interpretive_steps": 0,
      "relevance_strength": "DIRECT"
    },
    {
      "op": "LINK_EVIDENCE",
      "claim_id": "16e0b7e8-8f47-8f64-9012-637a9e7f19b5",
      "direction": "SUPPORT",
      "evidence_item_id": "frameshift_substitution_evidence",
      "interpretive_steps": 0,
      "relevance_strength": "DIRECT"
    }
  ],
  "outcome": "FOUND",
  "searched": "Read the open-access Nature Communications article, including abstract, Fig. 1 description, results on HEK293T reporter assays, and Fig. 4 substitution experiment. Searched the exact terms N1-methylpseudouridine, UUUC, UUCC, BNT162b2, mRNA-1273, HEK293T, and +1 frameshifting."
}

Rows created

• Source 572bf179-dd9b-8bf8-8cbb-77346d5eaf15
• SourceLocation 220d0ee2-d4d8-888d-9a0b-009e07ce62ba
• SourceLocation 18d76637-b19c-8df6-9307-7739c7a508a1
• SourceLocation 03ae8205-dee1-8b31-b103-092479988430
• EvidenceItem 403b8468-6f77-8c84-9e78-277c531bfd0f
• EvidenceItem fb46368e-693f-835e-837a-bfd083ad287f
• EvidenceItem 0cbe2f52-d9c3-8df0-b173-bc1d85824c23
• EvidenceClaimLink 95cc00e7-3ec4-8804-add8-1608a3b23777 (accepted seq 25830)
• EvidenceClaimLink 1fae645b-c9f3-896e-a80f-2a1cb8fe5806 (accepted seq 25830)
• EvidenceClaimLink 165b79b0-11e8-8b0b-8137-8526059a619f (accepted seq 25830)

Status history

Audits

None.

Audit sampling (audit-policy-v0.1): probability 1.0000, sampled yes; inputs {"n":"0.00","mean":"0.5000","domain":"general","task_type":"OPPOSING_EVIDENCE_SEARCH","principal_tier":"PSEUDONYMOUS","downstream_count":1,"outcome_is_unusual":false}