{
  "abstract": "NKG2D (encoded by KLRK1 in humans and Klrk1 in mice) is an activating receptor expressed by cytotoxic lymphocytes. In humans, NKG2D signaling is regulated post-transcriptionally: activated T cells retain intron 4 of KLRK1 to generate NKG2D-TR, a truncated dominant-negative isoform that limits receptor signaling. Whether mice, the principal preclinical model for NKG2D-directed therapies, possess an analogous regulatory mechanism remains unknown. Across four murine RNA-seq datasets comprising 50 samples and spanning T-cell differentiation, graft-versus-host disease, and acute and chronic LCMV infection, we examined the retained-intron isoform Klrk1-203. The transcript retains the canonical start codon, while its predicted stop codon lies within the terminal exon downstream of the final exon-exon junction, suggesting that it may escape nonsense-mediated decay. If translated, Klrk1-203 is predicted to encode a truncated product that retains the cytoplasmic and transmembrane domains but lacks most of the ligand-binding ectodomain. This predicted architecture resembles human NKG2D-TR, although the murine product contains a short C-terminal sequence encoded by the retained intron. Klrk1-203 was below the detection limit in unchallenged naive and early-effector T cells but was induced in differentiated effector and memory populations, reaching approximately one-fifth of total Klrk1 transcripts in one effector-memory sample. Read-level analyses independently demonstrated increased intron 4 retention with differentiation; however, short-read sequencing cannot fully distinguish Klrk1-203 from the co-retained Klrk1-204 transcript, making isoform-specific abundance dependent on model-based quantification. An independent coding-potential algorithm classified Klrk1-203 as non-coding, providing an important counterpoint to the structural predictions. Together, these findings identify Klrk1-203 as a candidate NMD-resistant, differentiation-associated regulator of murine NKG2D and a potential counterpart of human NKG2D-TR that warrants experimental validation.",
  "abstract_shown": true,
  "affiliations": [
    "SUNY Upstate Medical University,"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "I. H. Topkaya"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Karimi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/15zgn00bxmrmk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.21.746301",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.21.746301v2.full",
  "id": "15zgn00bxmrmk",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.21.746301v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|Immune Cell Function and Interaction"
    ]
  ],
  "openalex": "W7204242260",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.21.746301v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/15zgn00bxmrmk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:21Z",
      "native_id": "10.64898/2026.08.21.746301",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.21.746301v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Differentiation-coupled intron retention reveals a candidate NKG2D-TR-like isoform at the murine Klrk1 locus",
  "title_text": "Differentiation-coupled intron retention reveals a candidate NKG2D-TR-like isoform at the murine Klrk1 locus",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:21Z",
  "url": "https://research.draconitic.com/paper/15zgn00bxmrmk",
  "venue": "bioRxiv",
  "versions": []
}