RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae
RNA secondary structure mediates alternative 3′ss selection in Saccharomyces cerevisiae
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DOI：
10.1261/rna.030767.111
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发表时间：
2012-06-01
期刊：
影响因子：
4.5
通讯作者：
Eyras, Eduardo
中科院分区：
文献类型：
--
作者：
Plass, Mireya;Codony-Servat, Carles;Eyras, Eduardo
选择性剪接是前体 mRNA 中外显子的不同组合产生不同成熟 mRNA 的机制。该过程由剪接因子介导，剪接因子结合前体 mRNA 并影响对其剪接信号的识别。酵母菌缺乏后生动物中存在的许多调节因子。因此，通常认为选择性剪接的数量是有限的。然而，最近有令人信服的证据表明酵母具有功能性选择性剪接，主要是为了响应环境条件。我们之前已经证明前体 mRNA 的序列和结构特性可以解释酿酒酵母中 3' 剪接位点 (ss) 的选择。在这项工作中，我们扩展了之前的观察结果，构建了一个计算分类器，可以解释该生物体 CDS 和 5' UTR 中大部分带注释的 3's。此外，我们表明相同的规则可以解释替代 3 的选择。对许多预测的替代 3's 的实验验证表明，与带注释的 3's 相比，它们的使用率较低。大多数这些替代 3's 引入了提前终止密码子 (PTC)，表明在表达调节中发挥作用。此外，对温度影响的全基因组分析以及随后的实验验证仅产生少量变化，表明这种类型的调节并不普遍。我们的结果与酵母中由前体 mRNA 结构介导的替代 3's 选择的存在相一致，这种选择可以对温度等外部线索做出反应，并且可能与基因表达的控制有关。
Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 3' splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 3'ss in the CDS and 5' UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 3'ss. Experimental validation of a number of predicted alternative 3'ss shows that their usage is low compared to annotated 3'ss. The majority of these alternative 3'ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 3'ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression.