Differentiation-coupled intron retention reveals a candidate NKG2D-TR-like isoform at the murine Klrk1 locus
Topkaya, I. H.; Karimi, M. · immunology · 2026-09-04 · 原文
DOI：10.64898/2026.08.21.746301作者：2 位
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. Klrk1-2
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1. 人话版
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.
2. 领域脉络
本文类目：immunology，属于其所在研究脉络的最新进展。
3. 机制拆解
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.
4. 证据与数字
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.
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.
5. 反例与边界
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6. 跨领域连接与意外收获
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8. 术语表
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