Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, United States of America.
PLoS One. 2011;6(7):e21627. doi: 10.1371/journal.pone.0021627. Epub 2011 Jul 13.
Non-productive antigen receptor genes with frame shifts generated during the assembly of these genes are found in many mature lymphocytes. Transcripts from these genes have premature termination codons (PTCs) and could encode truncated proteins if they are not either inactivated or destroyed by nonsense-mediated decay (NMD). In mammalian cells, NMD can be activated by pathways that rely on the presence of an intron downstream of the PTC; however, NMD can also be activated by pathways that do not rely on these downstream introns, and pathways independent of NMD can inactivate PTC-containing transcripts. Here, through the generation and analysis of mice with gene-targeted modifications of the endogenous T cell receptor beta (Tcrb) locus, we demonstrate that in T cells in vivo, optimal clearance of PTC-containing Tcrb transcripts depends on the presence of an intron downstream of the PTC.
在这些基因的组装过程中产生的非生产性抗原受体基因，存在于许多成熟的淋巴细胞中。这些基因的转录本具有过早终止密码子（PTCs），如果它们不被无意义介导的衰变（NMD）灭活或破坏，则可以编码截断的蛋白质。在哺乳动物细胞中，NMD 可以通过依赖 PTC 下游内含子存在的途径被激活；然而，NMD 也可以通过不依赖这些下游内含子的途径被激活，并且独立于 NMD 的途径可以使含有 PTC 的转录本失活。在这里，通过生成和分析内源性 T 细胞受体 β（Tcrb）基因座基因靶向修饰的小鼠，我们证明在体内 T 细胞中，含有 PTC 的 Tcrb 转录本的最佳清除取决于 PTC 下游内含子的存在。
