Retelska Dorota, Iseli Christian, Bucher Philipp, Jongeneel C Victor, Naef Felix
Swiss Institute of Bioinformatics, Batiment Genopode, UNIL, 1015 Lausanne, Switzerland.
BMC Genomics. 2006 Jul 12;7:176. doi: 10.1186/1471-2164-7-176.
Cleavage of messenger RNA (mRNA) precursors is an essential step in mRNA maturation. The signal recognized by the cleavage enzyme complex has been characterized as an A rich region upstream of the cleavage site containing a motif with consensus AAUAAA, followed by a U or UG rich region downstream of the cleavage site.
We studied these signals using exhaustive databases of cleavage sites obtained from aligning raw expressed sequence tags (EST) sequences to genomic sequences in Homo sapiens and Drosophila melanogaster. These data show that the polyadenylation signal is highly conserved in human and fly. In addition, de novo motif searches generated a refined description of the U-rich downstream sequence (DSE) element, which shows more divergence between the two species. These refined motifs are applied, within a Hidden Markov Model (HMM) framework, to predict mRNA cleavage sites.
We demonstrate that the DSE is a specific motif in both human and Drosophila. These findings shed light on the sequence correlates of a highly conserved biological process, and improve in silico prediction of 3' mRNA cleavage and polyadenylation sites.
信使核糖核酸（mRNA）前体的切割是mRNA成熟过程中的一个关键步骤。切割酶复合物识别的信号的特征是，在切割位点上游有一个富含A的区域，其中包含一个共有序列为AAUAAA的基序，随后在切割位点下游有一个富含U或UG的区域。
我们利用通过将原始表达序列标签（EST）序列与人类和黑腹果蝇的基因组序列比对而获得的切割位点详尽数据库，对这些信号进行了研究。这些数据表明，聚腺苷酸化信号在人类和果蝇中高度保守。此外，从头基序搜索对富含U的下游序列（DSE）元件产生了更精确的描述，该元件在这两个物种之间表现出更大的差异。在隐马尔可夫模型（HMM）框架内应用这些精确的基序来预测mRNA切割位点。
我们证明DSE在人类和果蝇中都是一个特定的基序。这些发现揭示了一个高度保守的生物学过程的序列相关性，并改进了对3'mRNA切割和聚腺苷酸化位点的计算机预测。
