Arabidopsis 2010: Identification, Modeling, and Prediction of Arabidopsis thaliana mRNA 3'-processing Sites

转录后加工是基因调控的重要机制。这个项目涉及到mRNA的3‘-加工，这是一个包括前体RNA序列的切割和随后的聚腺苷酸化的过程。3‘-加工位点由顺式作用的信号元件决定，这些信号元件是未成熟前体mRNA中的短控制序列。酵母中的信号已经得到了很好的表征，但拟南芥中的信号才刚刚开始确定所需顺式元件的精确序列和定位特征。与选择性剪接类似，特定mRNA的交替3‘-加工是调节成熟mRNA序列的一种机制。然而，与备选剪接不同的是，备选3‘-加工通常只改变mRNA的3’-非翻译区(3‘-UTR)，而蛋白质编码序列保持不变。3‘-非编码区序列的变异会导致3’-非编码区特有的调控元件的改变，如mRNA的稳定性、翻译或定位元件。该项目的具体目标是：(1)建立一个经实验确定的拟南芥3‘-加工位点的精选数据库，(2)构建一个基于离散状态空间模型(DSM)的拟南芥mRNA3’-加工位点预测工具，以及(3)创建一个可自由访问的网络服务器接口，以连接数据库和预测工具。DSM模型是隐马尔可夫模型(HMM)的一种形式，其模型结构是手动设计的，而不是自动设计的。基于DSM的模型曾被用于预测酿酒酵母中的3‘-加工位点，它具有与植物中发现的类似的3’-加工控制元件。公开使用预测工具将使外部研究人员能够分析任何感兴趣的基因或基因组，即使在经过挑选的数据库中没有实验确定的位置的情况下也是如此。3‘-加工位点的预测也可以与基因预测软件相结合，使预测更加完整，包括可能的3’-非编码区序列。网址为：http://bmerc-www.bu.edu/polyA/.

Post-transcriptional processing of mRNA is an important mechanism of gene regulation. This project is concerned with 3'-processing of mRNA, a process that includes cleavage of the precursor RNA sequence and subsequent polyadenylation. 3'-processing sites are determined by cis-acting signal elements, short control sequences within the immature precursor mRNA. The signals in yeast have been well characterized, but those in Arabidopsis have only begun to identify the precise sequence and positioning characteristics of the required cis-elements.Alternative 3'-processing of a specific mRNA, similar to alternative splicing, is a mechanism for regulating the sequence of the mature mRNA. Unlike alternative splicing, however, alternative 3'-processing typically changes only the 3'-untranslated region (3'-UTR) of the mRNA, leaving the protein coding sequence unaltered. Variation of the 3'-UTR sequence results in altered regulatory elements specific to the 3'-UTR, such as mRNA stability, translation, or localization elements. The specific goals of this are project are: (1) establishment of a curated database of experimentally determined 3'-processing sites for Arabidopsis, (2) construction of a discrete state-space model (DSM) based predictive tool for Arabidopsis mRNA 3'-processing sites, and (3) creation of a freely accessible web server interface to both the database and the predictive tools. DSM models are a form of Hidden Markov Models (HMM), in which the model structure is manually, rather than automatically, designed. DSM based models have previously been used to predict 3'-processing sites in the yeast, Saccharomyces cerevisiae, which has 3'-processing control elements similar to those found in plants. Public access to predictive tools will make it possible for external researchers to analyze any gene or group of genes of interest, even in the absence of experimentally determined sites in the curated database. Prediction of 3'-processing sites can also be coupled with gene prediction software to make the prediction more complete, including probable 3'-UTR sequences. The web site is: http://bmerc-www.bu.edu/polyA/.