mRNA translation and decay are tightly interconnected processes both in the context of mRNA quality-control pathways and for the degradation of functional mRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions, and the recruitment of specific proteins to ribosomes is an important determinant of mRNA turnover. However, the extent to which translation-dependent mRNA decay (TDD) and translation-independent mRNA decay (TID) pathways participate in the degradation of mRNAs has not been studied yet. Here we describe a comprehensive analysis of basal and signal-induced TDD and TID in mouse primary CD4⁺ T cells. Our results indicate that most cellular transcripts are decayed to some extent in a translation-dependent manner. Our analysis further identifies the length of untranslated regions, the density of ribosomes, and GC3 content as important determinants of TDD magnitude. Consistently, all transcripts that undergo changes in ribosome density within their coding sequence upon T cell activation display a corresponding change in their TDD level. Moreover, we reveal a dynamic modulation in the relationship between GC3 content and TDD upon T cell activation, with a reversal in the impact of GC3- and AU3-rich codons. Altogether, our data show a strong and dynamic interconnection between mRNA translation and decay in mammalian primary cells.

中文翻译：

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T 细胞激活期间，翻译依赖性和非依赖性 mRNA 衰减通过由核糖体密度定义的相互排斥的途径发生

在 mRNA 质量控制途径和功能性 mRNA 降解的背景下，mRNA 翻译和降解是紧密相连的过程。通过密码子使用、核糖体碰撞和向核糖体募集特定蛋白质导致的共翻译 mRNA 降解是 mRNA 周转的重要决定因素。然而，翻译依赖性 mRNA 衰减 (TDD) 和翻译无关 mRNA 衰减 (TID) 途径参与 mRNA 降解的程度尚未研究。在这里，我们描述了对小鼠原代 CD4 ⁺ T 细胞中基础和信号诱导的 TDD 和 TID 的全面分析。我们的结果表明，大多数细胞转录本在某种程度上以翻译依赖性方式衰减。我们的分析进一步确定非翻译区的长度、核糖体的密度和 GC3 含量是 TDD 大小的重要决定因素。一致的是，在 T 细胞激活后，其编码序列内的核糖体密度发生变化的所有转录物都显示出相应的 TDD 水平变化。此外，我们揭示了 T 细胞激活时 GC3 含量与 TDD 之间关系的动态调节，以及富含 GC3 和 AU3 密码子的影响的逆转。总而言之，我们的数据显示哺乳动物原代细胞中 mRNA 翻译和衰变之间存在强大且动态的相互关联。