For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are larger for short-tailed mRNAs that have previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities.

中文翻译：

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细胞质 mRNA 代谢动力学。

对于除少数 mRNA 之外的所有 mRNA，新陈代谢的动态是未知的。在这里，我们开发了一个实验和分析框架，用于检查来自数千个基因的 mRNA 的这些动态。小鼠成纤维细胞的 mRNA 以不同的基因内和基因间 poly(A) 尾长度离开细胞核。一旦进入细胞质，它们就具有广泛（1000 倍）范围的去腺苷酸化速率常数，这对应于细胞质寿命。事实上，除了少数例外，降解似乎主要通过与去腺苷酸化相关的机制发生，而内切核酸酶切割或不依赖去腺苷酸化的脱帽几乎没有贡献。大多数 mRNA 分子只有在尾长低于 25 nt 后才会降解。短尾 mRNA 的衰减率常数变化很大（1000 倍），对于先前经历了更快去腺苷酸化的短尾 mRNA 来说更大。这种偶联有助于清除快速脱腺苷酸化的 mRNA，使大范围的脱腺苷酸化速率常数能够赋予类似大范围的稳定性。