Quantification of pre-mRNA escape rate and synergy in splicing.
Quantification of pre-mRNA escape rate and synergy in splicing.
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DOI：
10.1093/nar/gku1014
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发表时间：
2014-11-10
影响因子：
14.9
通讯作者：
Becskei A
中科院分区：
文献类型：
--
作者：
Bonde MM;Voegeli S;Baudrimont A;Séraphin B;Becskei A
剪接反应通常结合了联合收割机的高速度和准确性。然而，一些前体mRNA以保留的内含子逃离细胞核。内含子保留可以控制基因表达和增加蛋白质组多样性。我们计算了酵母PTC7内含子和前mRNA的逃逸率。这种预测是由剪接是一个线性过程的观察，并通过推导简单的代数表达式，从一个模型的共同和转录后剪接和RNA监视，确定无义介导的衰减（NMD）的前mRNA与保留的内含子的速度。逃逸率与观察到的剪接率阈值一致，低于该阈值，成熟mRNA水平下降。当mRNA含有多个内含子时，剪接的结果变得更加难以预测，因为不仅必须考虑前体mRNA的逃逸率，而且每个内含子的剪接受到其他内含子影响的可能性。我们发现SUS1 mRNA中的两个相邻内含子是协同剪接的，但这并不能抵消部分剪接的mRNA的逃逸。这些发现将有助于推断启动子活性，预测剪接调控网络的行为和控制。
Splicing reactions generally combine high speed with accuracy. However, some of the pre-mRNAs escape the nucleus with a retained intron. Intron retention can control gene expression and increase proteome diversity. We calculated the escape rate for the yeast PTC7 intron and pre-mRNA. This prediction was facilitated by the observation that splicing is a linear process and by deriving simple algebraic expressions from a model of co- and post-transcriptional splicing and RNA surveillance that determines the rate of the nonsense-mediated decay (NMD) of the pre-mRNAs with the retained intron. The escape rate was consistent with the observed threshold of splicing rate below which the mature mRNA level declined. When an mRNA contains multiple introns, the outcome of splicing becomes more difficult to predict since not only the escape rate of the pre-mRNA has to be considered, but also the possibility that the splicing of each intron is influenced by the others. We showed that the two adjacent introns in the SUS1 mRNA are spliced cooperatively, but this does not counteract the escape of the partially spliced mRNA. These findings will help to infer promoter activity and to predict the behavior of and to control splicing regulatory networks.
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