RNA stability, important for eukaryotic gene expression, is thought to depend on deadenylation rates, with shortened poly(A) tails triggering decapping and 5' to 3' degradation. In contrast to this view, recent large-scale studies indicate that the most unstable mRNAs have, on average, long poly(A) tails. To clarify the role of deadenylation in mRNA decay, we first modeled mRNA poly(A) tail kinetics and mRNA stability in yeast. Independent of deadenylation rates, differences in mRNA decapping rates alone were sufficient to explain current large-scale results. To test the hypothesis that deadenylation and decapping are uncoupled, we used rapid depletion of decapping and deadenylation enzymes and measured changes in mRNA levels, poly(A) length and stability, both transcriptome-wide and with individual reporters. These experiments revealed that perturbations in poly(A) tail length did not correlate with variations in mRNA stability. Thus, while deadenylation may be critical for specific regulatory mechanisms, our results suggest that for most yeast mRNAs, it is not critical for mRNA decapping and degradation.

中文翻译：

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脱帽引发的 RNA 降解在很大程度上与最初的脱腺苷化无关。


RNA 稳定性对于真核基因表达很重要，被认为取决于脱腺苷化率，缩短的聚腺苷酸尾会触发脱帽和 5' 至 3' 降解。与这一观点相反，最近的大规模研究表明，最不稳定的 mRNA 平均具有长聚腺苷酸尾。为了阐明脱腺苷酸化在 mRNA 衰减中的作用，我们首先模拟了酵母中 mRNA 多聚 (A) 尾动力学和 mRNA 稳定性。与脱腺苷化率无关，仅 mRNA 脱帽率的差异就足以解释当前的大规模结果。为了检验脱腺苷化和脱腺苷酸不偶联的假设，我们使用了脱腺苷酸化酶和脱腺苷酸化酶的快速消耗，并测量了转录组范围内和单个报告基因的 mRNA 水平、poly(A) 长度和稳定性的变化。这些实验表明，poly(A) 尾长的扰动与 mRNA 稳定性的变化无关。因此，虽然去腺苷化对于特定的调控机制可能至关重要，但我们的结果表明，对于大多数酵母 mRNA 来说，它对于 mRNA 脱帽和降解并不重要。