Xiao Xinshu, Wang Zefeng, Jang Minyoung, Burge Christopher B
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18583-8. doi: 10.1073/pnas.0707349104. Epub 2007 Nov 12.
Accurate and efficient splicing of eukaryotic pre-mRNAs requires recognition by trans-acting factors of a complex array of cis-acting RNA elements. Here, we developed a generalized Bayesian network to model the coevolution of splicing cis elements in diverse eukaryotic taxa. Cross-exon but not cross-intron compensatory interactions between the 5' splice site (5'ss) and 3' splice site (3'ss) were observed in human/mouse, indicating that the exon is the primary evolutionary unit in mammals. Studied plants, fungi, and invertebrates exhibited exclusively cross-intron interactions, suggesting that intron definition drives evolution in these organisms. In mammals, 5'ss strength and the strength of several classes of exonic splicing silencers (ESSs) evolved in a correlated way, whereas specific exonic splicing enhancers (ESEs), including motifs associated with hTra2, SRp55, and SRp20, evolved in a compensatory manner relative to the 5'ss and 3'ss. Interactions between specific ESS or ESE motifs were not observed, suggesting that elements bound by different factors are not commonly interchangeable. Thus, the splicing elements defining exons coevolve in a way that preserves overall exon strength, allowing specific elements to substitute for loss or weakening of others.
真核生物前体mRNA的准确高效剪接需要反式作用因子识别一系列复杂的顺式作用RNA元件。在此，我们开发了一种广义贝叶斯网络来模拟不同真核生物类群中剪接顺式元件的共同进化。在人类/小鼠中观察到5'剪接位点（5'ss）和3'剪接位点（3'ss）之间存在跨外显子而非跨内含子的补偿性相互作用，这表明外显子是哺乳动物中的主要进化单位。所研究的植物、真菌和无脊椎动物仅表现出跨内含子相互作用，这表明内含子定义驱动了这些生物体中的进化。在哺乳动物中，5'ss强度和几类外显子剪接沉默子（ESSs）的强度以相关方式进化，而特定的外显子剪接增强子（ESEs），包括与hTra2、SRp55和SRp20相关的基序，相对于5'ss和3'ss以补偿方式进化。未观察到特定ESS或ESE基序之间的相互作用，这表明由不同因子结合的元件通常不可互换。因此，定义外显子的剪接元件以一种保持整体外显子强度的方式共同进化，允许特定元件替代其他元件的缺失或减弱。
