A computational analysis of sequence features involved in recognition of short introns
A computational analysis of sequence features involved in recognition of short introns
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DOI：
10.1073/pnas.201407298
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Burge, CB
中科院分区：
文献类型：
--
作者：
Lim, LP;Burge, CB
核前 mRNA 剪接机制对短内含子的剪接被认为是通过“内含子定义”机制进行的，其中 5' 和 3' 剪接位点（分别为 5' ss、Tss）最初被识别并跨内含子配对。在这里，我们描述了通过使用来自具有完整或接近完整基因组序列的五种真核生物的可用转录数据，对涉及短内含子识别的序列特征进行计算分析。利用信息论的方法测量了五个不同转录本特征的信息含量，并使用蒙特卡罗模拟来确定准确识别每个生物体中的短内含子所需的信息量。我们得出的结论是：(i) 果蝇和秀丽隐杆线虫中的短内含子基本上包含剪接机制识别的所有信息，并且模拟剪接特异性的计算机程序可以预测这两种生物体中大约 95% 的短内含子的确切边界； (it) 在酵母中，5' ss、分支信号和 3' ss 可以准确识别内含子位置，但不能精确确定每个内含子中 3' 切割的位置； (iii) 5' ss、分支信号和 3' ss 不足以准确识别植物和人类转录本中的短内含子，但可以在人类和拟南芥中识别候选内含子增强子基序的特定子集，这极大地提高了剪接模拟器的准确性。
Splicing of short introns by the nuclear pre-mRNA splicing machinery is thought to proceed via an "intron definition" mechanism, in which the 5 ' and 3 ' splice sites (5 ' ss, Tss, respectively) are initially recognized and paired across the intron. Here, we describe a computational analysis of sequence features involved in recognition of short introns by using available transcript data from five eukaryotes with complete or nearly complete genomic sequences. The information content of five different transcript features was measured by using methods from information theory, and Monte Carlo simulations were used to determine the amount of information required for accurate recognition of short introns in each organism. We conclude: (i) that short introns in Drosophila melanogaster and Caenorhabditis elegans contain essentially all of the information for their recognition by the splicing machinery, and computer programs that simulate splicing specificity can predict the exact boundaries of approximate to 95% of short introns in both organisms; (it) that in yeast, the 5 ' ss, branch signal, and 3 ' ss can accurately identify intron locations but do not precisely determine the location of 3 ' cleavage in every intron; and (iii) that the 5 ' ss, branch signal, and 3 ' ss are not sufficient to accurately identify short introns in plant and human transcripts, but that specific subsets of candidate intronic enhancer motifs can be identified in both human and Arabidopsis that contribute dramatically to the accuracy of splicing simulators.