Unit CNRS 7276 - INSERM U1262 - Limoges University, 2 rue du Docteur Marcland, 87025 Limoges, France.
Present address: Segal Cancer Center, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montréal, QC H3T 1E2, Canada.
Int J Mol Sci. 2020 Feb 17;21(4):1335. doi: 10.3390/ijms21041335.
The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid the synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Thus, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphocytes.
存在于转录本中的提前终止密码子（PTC）对细胞是危险的，因为它们编码潜在有害的截短蛋白，这些蛋白可能具有显性负或获得性功能效应。为了避免这些缩短的多肽的合成，可以激活几种 RNA 监测系统来降低含有 PTC 的 mRNA 的水平。无义介导的 mRNA 降解（NMD）通过使用几个关键的 NMD 因子（如移框（UPF）蛋白）来确保含有 PTC 的 mRNA 的快速降解。另一种途径称为无义相关的可变剪接（NAS），通过选择性剪接上调跨越干扰 PTC 的转录本。因此，这些 RNA 质量控制过程通过正反馈和负反馈从细胞中消除含有异常 PTC 的 mRNA。在这篇综述中，我们描述了 NMD 和 NAS 的一般机制，以及它们各自在淋巴细胞中异常免疫球蛋白和 TCR 转录本降解中的参与。
